Accretive real-life testing of new drugs in small, targeted patient populations, with initially restricted licences expanding to accommodate new evidence of effectiveness, could eventually render the current development model of Phase I-IV clinical trials obsolete, a new report predicts.
This movement towards a “complete integration of clinical trials with clinical practice, as is already starting to happen in the treatment of cancer” is envisaged in a new report by PricewaterhouseCoopers (PwC), Pharma 2020: The Vision – Which Path Will You Take? By 2020, it contends, new medicines will be available through “live licences contingent on the performance of extensive in-life testing, including trials in specific patient sub-populations, and a predetermined scheduled for reviewing each set of results.”
In other words, the report says, “every medicine on the market will have a pre-arranged, fully automated pathway through its lifecycle, and its development will be a continuous process rather than ending when it is approved.”
While technological advances such as biomarkers and ‘pervasive healthcare’ – the use of remote devices to monitor patients on a real-time basis wherever they are, allowing drugs to be testing outside the clinical setting – will help to refine this process, the shift towards continuous development will also be driven by the urgent need for industry to make safer, more effective (and more individualised) treatments more economically, PwC points out.
“The pharma industry will not be in a strong position to capitalise on opportunities unless R&D productivity improves,” commented Dr Steve Arlington, PwC’s global pharmaceutical research and development advisory leader and principal author of the report. “The industry is investing twice as much in R&D as it was a decade ago to produce two-fifths of the new medicines it then produced. It is simply an unsustainable business model.”
Current model 'inflexible and highly empirical
PwC cites criticisms by Dr Scott Gottlieb, former deputy commissioner for medical and scientific affairs at the US Food and Drug Administration (FDA), of the inflexible, highly empirical model of clinical development that currently predominates, generating information “about how large populations with the same or similar conditions are likely to respond to treatment.”
The development of biomarkers to stratify patients with related but distinct conditions will enable pharmaceutical companies “to make different treatments for different patient sub-populations, test only in patients who suffer from those conditions, and thus reduce both the number and size of the trials required to prove efficacy,” the report says.
In the new development model, it predicts, a company will start by defining the minimum amount and type of information it needs to secure approval for in-life testing of a new medicine. It will then run a series of small, highly targeted clinical studies, using simulation, modelling and other techniques, to ensure it understands the product’s efficacy and safety, before submitting the data to a regulatory agency.
If the regulator is satisfied with this evidence, it will issue a ‘live licence’ permitting the sponsor to market the drug on a very restricted basis. The company will follow up by conducting in-life trials of the product in a small patient population. Whenever the sponsor adds substantively to the evidence of the drug’s safety and effectiveness, PwC explains, the licence will be extended to cover a larger or different patient population or multiple indications.
Cutting and recouping costs
Not only would this approach cut development expenditure even further, it would also allow pharmaceutical companies to recoup some of their costs more quickly, enabling them in turn to charge lower prices for new therapies, the report suggests. Moreover, it would facilitate testing for polypharmacy in wider populations and “align the bench and the bedside more closely. So, for example, a patient who suffered from diabetes and lived in Paris would be automatically given the opportunity to enrol in clinical trials in the area at the same time as receiving treatment.”
The FDA and the European Medicines Agency have already shown they are willing to grant conditional approvals for some therapies, such as orphan drugs and treatments for life-threatening conditions, PwC observes.
For industry, though, early approval would not come without a trade-off. As the legislation governing new medicines and the way they are licensed becomes more complex, the report comments, “the regulators will insist on greater collaboration and expect to be consulted on a regular basis from a much earlier point in development."