Scientists are suggesting that scientific and political changes may make adaptive pathways the preferred approach for approving new treatments.
“Adaptive pathways should be the preferred approach in the near future to bring new medicines to patients.” A number of scientists – including members of the European Medicines Agency (EMA) and its scientific committees – take this position in a co-authored article published in Clinical Pharmacology & Therapeutics. The concept of adaptive pathways foresees either an initial approval in a well-defined high-medical-need subgroup and subsequent widening of the indication to a larger patient population, or an early (perhaps conditional) approval that is prospectively planned and where uncertainty is reduced through postapproval data collection. Within the article (entitled ‘From adaptive licensing to adaptive pathways: delivering a flexible life-span approach to bring new drugs to patients’), the authors – who are part of the New Drug Development Paradigm initiative – analyse the key drivers for adaptive licensing. These include:
- patients’ demands for timely access to medicines, in particular where there are unmet medical needs. With adaptive licensing, new treatments would be made available to some patients earlier, on a smaller evidence base, if efficacy has been observed in this patient population.
- a better understanding of the pathologies that have led to the identification of subgroups of patients who are likely to respond better to certain medicines than others. For many of these subgroups, a progressive approach to licensing while learning from real-world experience may become the only viable access route to new treatments.
- the growing financial pressure on healthcare systems and a call for the more targeted use of medicines to increase their therapeutic value.
- the pressure on the industry to make the development of medicines, in particular for chronic diseases, sustainable. Development programmes targeting smaller better-defined populations would lower the threshold for financing a drug’s development and allow for more medicines to be brought forward.
A number of recent developments are fostering the transition from a traditional approach – which implies large trials and marketing authorisations for use in broad groups of patients – to an adaptive approach. These include the development of innovative clinical trial designs, learning healthcare systems and the inclusion of patients in decisionmaking processes to better understand the level of uncertainty they are willing to accept.
EMA launched a pilot project in March 2014 to explore this approach with real medicines in development. Soon after, the name of the pilot project was changed from adaptive licensing to adaptive pathways, to better reflect the idea of a life-span approach to bringing new medicines to patients, where clinical drug development, licensing, reimbursement, utilisation in clinical practice and monitoring are all viewed as part of a continuum. On 23 December 2014, the EMA published an update on the status of the adaptive pathways pilot project:
under the first phase of the project (to the beginning of December 2014), the EMA received 34 requests from companies to include their medicines in the adaptive pathways pilot project
- six of these requests concerned an advanced therapy medicinal product (ATMP), 12 were for orphan medicines and 11 came from small or medium-sized companies
- the medicines covered a broad range of therapeutic areas; 14 requests related to cancer indications.
Following review and discussion with the companies, six medicines have so far been selected to go forward for more in-depth discussions involving all stakeholders, including health technology assessment (HTA) bodies and patients’ representatives.
The first of these in-depth discussions, on the quality aspects of an ATMP, took place in December 2014 and others are planned for 2015. Stage I of the pilot project will close on 28 February 2015. Although the EMA will then focus on Stage II (including the in-depth discussions with applicants for the selected applications), after 28 February the EMA will still consider new applications for Stage II face-to-face meetings if the HTA and real world data collection aspects are well developed: applicants should contact the EMA for advice on the content and suitability of their request. A full review of the outcome and impact of the adaptive pathways pilot project will be conducted once at least six medicines selected for the pilot project have completed a procedure of parallel scientific advice with HTA bodies.