Table 3.

Opportunities and challenges of treatment optimization studies that were named by the interviewees. Note that some points can be considered as both an opportunity and a challenge, depending on which stakeholder's perspective one chooses to adopt (e.g. increased drug prices can be beneficial to the industry but detrimental to patients).

Opportunities	Challenges
Patients would benefit directly from its results, since its objectives and outcomes measures were selected based on their relevance for clinical practice	The financing of such studies poses a challenge, especially since they will likely have to run over a long period of time and include a large number of participants: sponsoring by the industry could allow them to influence the trial setup and increase their drug prices, while public funding could be seen as a double payment and an unacceptable shift of the financial burden linked with developing new drugs toward the public
It could improve HTA and payer decision-making through prevention or identification of inappropriate reimbursement decisions, thereby decreasing costs and increasing healthcare spending efficiency	The industry might not want to be involved if the probability of a favorable outcome for their drugs is too low, given the loss of revenue such initiatives could cause
It could improve clinical decision-making by providing physicians with evidence that a therapy works when it is applied in real-world conditions, as well as with information on how it should be administered to achieve the best results	Clinicians might not be willing to participate due to the additional burden imposed on them, their inexperience with this kind of research and the lack of interest on the part of high-impact scientific journals to publish its results
It could give manufacturers' products a major marketing advantage over those of their competitors, which could translate into higher prices, more favorable reimbursement conditions, and an increased uptake by clinicians	No general framework surrounding the optimal design and methodological features of such studies has been created yet, and the associated uncertainties can only be managed through the use of larger sample sizes, the development of quality standards, and other measures of this kind
It could lead to the registration of additional indications in specific subpopulations and generate new combinations of active substances, resulting in the broader application of drugs in clinical practice	The infrastructure needed to perform these studies in a multi-stakeholder and potentially international manner is currently not yet available and could potentially give rise to conflicts of interest
It would allow us to identify and reward those medicines that have an added clinical value compared to existing alternatives, which could discourage the development of me-too drugs with little additional benefit	It could be complicated by legal issues relating to who is liable if unexpected side effects occur when the therapy is used in ways that have not been previously approved, or to who should be able to request changes to the label if the findings of the study warrant such modifications
It could help fill the evidence gaps that are left by the conventional registrational trials at the end of the clinical development program	Its optimal timing remains unclear: in the pre-approval setting, it could delay marketing authorization and therefore patient access, while in the post-authorization environment, its findings may come too late to influence regulatory or payer decision-making