Table 2.

Transitions that are required to move from a conventional scenario to an adaptive licensing (adaptive pathways) scenario

Conventional scenario	Adaptive licensing scenario
Single gated licensing decision The life span of a technology is clearly divided into a pre‐ and a post licensing phase by the moment of marketing authorization.6	Life span management AL acknowledges that knowledge continues to accumulate after a license is granted and that access is best addressed by repeat cycles of “learning‐confirming‐(re)licensing.” Early engagement of decision makers enables integrated planning of drug development, licensing, reimbursement (coverage), utilization in clinical practice, and monitoring of treatment outcome. The life‐span management is expected to lead to lower realized risks for patients compared to the current approach—in spite of smaller data packages early on.
Prediction Historically, once a drug was authorized, regulators had limited power to monitor performance or influence real‐life use of the drug. This was a responsible justification for demanding high evidence standards in order to predict a drug's performance in the market place. Analogous considerations applied to coverage decisions.	Monitoring Regulators in several jurisdictions have been granted substantial new authorities in postlicensing surveillance and risk mitigation; the tools for monitoring real‐world performance (e.g., registries, e‐medical records, postauthorization efficacy studies, methodology to address confounding) are improving, effectively providing a basis for a life‐span approach to marketing authorization. Analogous considerations apply to coverage decisions.
RCT only In many therapeutic areas, information from RCTs is almost exclusively the basis for regulatory decisions; information from nonrandomized studies is often not considered robust enough by regulators and sometimes by payers (exceptions may be orphan medicines and postlicensing safety studies).	Toolkit for evidence generation The entire toolbox of knowledge generation is used to underpin regulatory and coverage decisions, including conventional RCTs, real‐world (pragmatic) RCTs, and all variations of (nonrandomized) observational studies. Real‐world evidence gains importance to inform postinitial rounds of licensing and coverage. Key is identifying prospectively situations where non‐RCT studies can be convincing.
Broad populations Sponsors often aim to obtain as broad as possible an initial license. Effects in identifiable subgroups that are nested within the broad population may (if at all) be addressed subsequently, often for purposes of differentiation against incoming competitor products.	Targeted populations An adaptive approach would initially aim to show positive benefit–risk and added value in a defined subpopulation, followed by additional clinical trials and studies in other subpopulations that would lead to gradual widening (or restricting) of the label and the covered populations, as supported by new data.
Focus on licensing Obtaining a marketing authorization is the primary goal of sponsors, considerations of (payer) access follow later.	Focus on patient access The information needs of all decision makers (including regulators, payers, providers, and patients) are considered from the start and, where possible, are aligned to enable efficient drug development and timely access; patients are increasingly involved in decision making.
Open utilization Physicians have near‐complete freedom of prescribing drugs off‐label, without evidence generation.	Targeted utilization Greater emphasis by regulators, payers, and industry on targeted drug utilization in the marketplace and on mitigating off‐label use; with a view to ensure safe use, continued learning, and cost‐effectiveness.

AL: adaptive licensing; RCT: randomized controlled trial.