Clinical Trials Due an Overhaul to Conquer the Pharma "Valley of Death"

Costs associated with drug development have risen from around $138m in 1975 to over $1 billion in 2005, with clinical trials representing a key factor in this increasing expenditure, according to a new report by healthcare industry experts GBI Research.

The new research* looks at why researchers in the pharma industry now refer to the clinical development process as the ‘valley of death’, which must be crossed to attain drug approval.
Clinical trials have grown longer and more complex, while volunteer enrolment and retention rates have fallen. More than 30% of experimental drugs that reach Phase III fail at this point. Late stage failures are costly to the industry - Pfizer’s torcetrapib, which failed its Phase III trial in 2006, led to the value of Pfizer dropping by $21 billion overnight, and 10,000 job losses being announced the following year.

Recent analyses show that this problem has grown in recent years. Overall, clinical approval success rates have fallen to approximately 16%, though this figure varies widely by therapeutic area. Pivotal trial and regulatory failures were recorded for 31 drugs in 2011, with Eli Lilly, Bristol-Myers Squibb, AstraZeneca, Merck, Sanofi, Novartis and GlaxoSmithKline all suffering at least one setback.

The most common reason for drug failure during Phase II development is a lack of efficacy as determined by primary endpoints. Phase III failures tend to be in therapeutic areas that may provide a higher chance of approval and reimbursement, such as cancer or neuroscience. Whilst it is tempting to speculate that drug development is more difficult for drugs with novel mechanisms of action in these areas of unmet need, this data implies that the pressure on companies to keep development pipelines full may also have led to compounds advancing into Phase III on the basis of inadequate or marginal proof-of-concept.

Others have argued that the majority of failures in clinical trials are due to the inadequacy of animal models to predict success in humans, implying a fundamental flaw in drug development processes which use animal testing methods.

It is essential that R&D productivity is improved, and the ‘quick win, fast fail’ model is being touted as a possible way to achieve this. This model argues that investments made early in the process increase the information available on which to base key decisions, enabling the earlier termination of projects prior to huge investments being made for the Phase III program.