Health Technology Assessment in the Context of Adaptive Pathways for Medicines in Europe: Challenges and Opportunities.

Adaptive pathways for medicines have gained momentum and, in Europe, adaptive pathways have recently been introduced into the European Medicines Agency (EMA) processes after a successful 2-year pilot. Although the concept, as initially proposed, contained several elements that would have required regulatory reforms, the adaptive pathways program has developed a more pragmatic scope (Box 1). In this article, we explore the main challenges and opportunities adaptive pathways pose from a European health technology assessment (HTA) perspective.

From adaptive licensing to adaptive pathways: delivering a flexible life-span approach to bring new drugs to patients.

The concept of adaptive licensing (AL) has met with considerable interest. Yet some remain skeptical about its feasibility. Others argue that the focus and name of AL should be broadened. Against this background of ongoing debate, we examine the environmental changes that will likely make adaptive pathways the preferred approach in the future. The key drivers include: growing patient demand for timely access to promising therapies, emerging science leading to fragmentation of treatment populations, rising payer influence on product accessibility, and pressure on pharma/investors to ensure sustainability of drug development. We also discuss a number of environmental changes that will enable an adaptive paradigm. A life-span approach to bringing innovation to patients is expected to help address the perceived access vs. evidence trade-off, help de-risk drug development, and lead to better outcomes for patients.

Accelerated access to innovative medicines for patients in need.

There is broad agreement among health-care stakeholders that more must be done to ensure that patients have timely access to new and innovative medicines. Assuming that industry will continue to develop such medicines at a sustainable rate, regulators and payers become the gatekeepers. Regulators, starting in the late 1980s/early 1990s, and, more recently, payers have implemented a variety of early-access pathways or initiatives, and this practice is continuing even today. This article describes the specific approaches that have been taken in four economically developed regions, reviews their success rates, and suggests possible new directions.

Localization of CAM II kinase-alpha, GAD, GluR2 and GABA(A) receptor subunit mRNAs in the human entorhinal cortex.

The human entorhinal cortex (ERC) is an important relay between neocortical association areas and the hippocampus. Pathology in this area, including disturbances in its unique cytoarchitecture and alterations in neurotransmitter receptor binding, has been implicated in several neuropsychiatric disorders but details of the patterns of gene expression for molecules involved in the major neurotransmitter systems in this cortex have been lacking. We used in situ hybridization histochemistry to localize the mRNAs for several proteins which are involved in excitatory and inhibitory neurotransmission in the human ERC. Labelling of mRNA for a glutamate receptor subunit (GluR2) and for a marker of glutamatergic cortical neurons (alpha type II calcium/calmodulin-dependent protein kinase) were distributed in a laminar manner which matched the cellular packing seen on the Nissl sections, with particularly high levels of labelling in the layer II (pre-alpha) cell clusters characteristic of this cortex. Cells labelled for the mRNA of 67 kDa glutamic acid decarboxylase, the synthesizing enzyme of GABA, were distributed diffusely throughout all layers, not concentrated in the cell clusters, and were present in higher numbers in layer III. The labelling of mRNAs for the alpha1, beta2 and gamma2 subunits of the GABA(A) receptor, however, was distributed in a laminar pattern similar to that for GluR2 and CAM II kinase mRNAs, implying a high concentration of inhibitory synapses on the excitatory cells which express these mRNAs.