Outsourcing-Pharma: Focus on Phase IIIB-IV research
Phase IIIB-IV research booming
20 per cent annually, compared with only 7 per cent for Phase
II-III research, driven by a surge in public drug safety concerns
and increased drug market competitiveness.
A >Tufts University report supports the trend, reporting that over 73 per cent of New Drug Applications (NDAs) are now associated with at least one Phase IV research commitment, a number that has doubled over the last five years.
Phase IIIB-IV spending is predicted to rise from $3.7bn (€3.1 bn) in 2004 to over $5bn in 2008 and as over half this type of research is outsourced, this is particularly good news for contract research organisations (CROs).
Two factors are fuelling this fire; evaporating drug pipelines; and the spate of recent high-profile drug recalls, culminating in the dramatic withdrawl in 2004 of prescription painkiller Vioxx, after an independent retrospective study of the drug raised cardiovascular safety concerns that were confirmed in subsequent Phase IIIB and IV studies.
Vioxx had been available on the market for five years and was being used to treat millions of patients before these safety concerns finally led to its swift withdrawl.
Since the drama with Vioxx, it's manufacturer, Merck, has had 9,650 lawsuits filed against it and incurred around $970 m in legal costs so far and in order to ride out the storm has had to resort to ongoing cost-cutting measures, including slashing 7,000 jobs.
The fall-out from Vioxx not only knocked the wind out of Merck's sails, but resonated throughout the pharma industry and left patients and doctors calling for more information to be made available on the risks and benefits of prescription drugs.
Ina move to avoid a similar scenario, and satisfy public demands, drug companies are now increasingly using Phase IIIB and IV studies, often simultaneously, as a way of both solidifying and expanding the scientific basis and safety of their product claims.
One particular area to come under scrutiny in the US after Vioxx has been direct to consumer advertising (DTC).
The practice is seen as highly controversial because it is used by drug companies purely to boost sales, and in doing so, can influence patients inappropriately and effectively bypass the physician as the primary influencer of drug prescribing.
According to Dr Hugo Stephenson, president of strategic research services at >Quintiles, many more patients were on Vioxx than should have been due to strong demand for the product placed on doctors by patients after responding to consumer advertising.
"This made the fallout even greater when the product was recalled due to the sheer volume of patients taking it," Stephenson told www.Outsourcing-Pharma.com.
"As a result, many drug companies are now taking a more cautious approach to DTC. Bristol-Myers Squibb, for example, has made a public commitment to not do any DTC marketing of a drug within its first year on the market," he said.
As part of their new approach, US drug companies are now looking for more concrete and meaningful clinical evidence to use in their DTC advertising campaigns and are turning to Phase IIIB-IV research to provide this.
Often these studies are taking place while new drug are still undergoing regulatory approval, so there is no precious time lost in getting the drug to market.
Once a manufacturer applies for marketing approval on a drug, all subsequent research that is not conducted in-line with the product approval is termed Phase IIIB.
Pre-approval Phase IIIB occurs while the product is still in regulatory approval and usually serves to provide extra information to support the drug when it is launched, such as comparative efficacy against competitor drugs.
Post-approval Phase IIIB research investigates the use of a drug outside its approved product indication to explore future new therapeutic opportunities.
Phase IV research, however, investigates products during or after marketing approval in line with their approval labels and are used to address questions about comparative efficacy, tolerability, safety and cost effectiveness of different treatment approaches.
Another major factor in the growth of Phase IIIB-IV clinical research is that as pipelines are drying up, drug companies are searching for new indications for their existing drugs, and are using Phase IIIB-IV clinical research strategically for this purpose.
In addition, one side-effect of this tough industry climate is that doctors and government authorities are being bombarded by sales reps trying to sell their drug as "the best," causing those on the receiving end to become increasingly wary and confused.
In order to stand out, drug companies are having to become more competitive in their promotional and advertising messages and are using Phase IIIB-IV studies to dig for a new marketing edge.
Looking forward, sharpened public awareness and the tough market atmosphere looks set to continue to spark these post-approval studies and CROs who can provide these services at a competitive cost are poised to benefit.
