An extensive new report issued by the World Health Organization (WHO) calls on global regulatory bodies to refine and improve their respective systems for approving new medicines, balancing the needs of public health and innovation to "ensure a continuous flow of the new medicines most needed by society."
The report, Priority Medicines for Europe and the World Update Report, 2013, is a follow-up to a 2004 report by the same name, and was prompted by the European Union calling for an update to the report to inform the development of their Horizon 2020 combined research program.
While the extensive report touches on a huge range of subjects, it devotes one section specifically to regulatory topics, noting that an optimally functioning regulatory system must balance three key considerations:
- speed of access versus excessive caution
- too few incentives and ones that promote expenditures on unnecessary innovations
- too little regulation and a stranglehold of regulation
In each example, the former represents the extreme of a laissez-faire system in which a regulator takes a hands-off approach, allowing the market - as well as unscrupulous actors - to act on its own accord. In the latter examples, a regulator acts with too much vigor, stifling innovation and market access.
WHO noted a sense of balance is especially pertinent given regulators' desire to implement adaptive approaches that permit tentative approvals based on preliminary data, often from Phase II clinical trials.
"These adaptive approaches are all based on the premise that knowledge about medicines is not binary, but continues to evolve over time," WHO explained. "The proposal is to replace the single transition from non-approval to approval with a series of approval stages with iterative phases of evidence gathering and regulatory evaluation. The use of adaptive approaches, which also incorporate elements of existing pathways, should be seen as a holistic option in the future regulatory system."
But while it may be a holistic option, WHO said its attractiveness does not diminish a number of challenges associated with its use, including the necessity to conduct follow-up trials and monitoring the patient population for which the product has obtained tentative approval.
The WHO report goes on to note four "Research priorities" that it recommends be pursued by global regulatory authorities.
The first of the priorities is a call to "develop and pilot new methods for evidence generation and benefit:risk assessment." Such processes could result in more efficient clinical testing using surrogate endpoints, adaptive designs or more structured benefit:risk instruments, WHO noted. "The aim is to increase the consistency and transparency of benefit-risk assessments and thereby the predictability of the marketing authorization procedure," it added.
The second recommendation calls for wider use of assessments to determine the expectations and performance of new regulations, including their cost-effectiveness. While this is already done in some markets, including the US, it is not done in many others, preventing comparative studies of various regulatory approaches.
Third, WHO calls for regulators to work collaboratively with one another and other "key actors" such as pharmaceutical companies, health technology assessment bodies, patients and healthcare providers.
Fourth (and similar in nature to the second recommendation), WHO recommends investing in what it calls "sharing and analysis of regulatory datasets for system evaluation."
"Regulations play a critical role in balancing people's expectations for new medicines to address unmet medical needs against the need to ensure that medicines are efficacious and have a positive benefit-risk ratio," WHO explained. "For regulators and companies to adapt to a changing world, research on the regulatory process is needed."
The main report is also supported by a background paper specifically on regulatory policy, which expands upon the points made in far greater detail. That paper is available on WHO's website here.
Priority Medicines for Europe and the World Update Report, 2013
WHO Report Index
WHO Press Release