title: The role of “Managed Entry Agreements” in managing the market entry of new, high-cost, cancer medicines. The determinants and the impact of agreements implemented in Australia, England, Scotland and Sweden, as part of Health Technology Assessment processes
Creators: name: Efthymiadou, Anastasia Olga
Publisher: name: London School of Economics and Political Science (LSE)
Year: 2022

description: Background: Managed Entry Agreements (MEAs) are increasingly used in the reimbursement negotiations of new, high-cost medicines, especially in oncology, to address evidentiary uncertainties in Health Technology Assessment (HTA) decision-making, due to immature evidence on their clinical and cost-effectiveness. Despite the growing interest in MEAs, the decision-making factors that determine their uptake remain unclear, while empirical evidence about their role in enhancing access to medicines also remains scarce. 
Objectives: The objectives of this thesis were three-fold: (i) to understand the extent to which the uptake of MEAs for cancer medicines differs across countries and why; (ii) to study the HTA variables that drive the uptake and different types of MEAs implemented across settings; and (iii) to evaluate the impact of implemented MEAs on improved availability of and timely access to cancer medicines. 
Methods: Data from publicly available HTA reports of oncology medicines approved between 2009 and 2018 in Australia, England, Scotland, and Sweden were collected as follows: 1) Social value judgements (SVJs), 2) Clinical/Economic evidence submitted, 3) Interpretation of this evidence (i.e., uncertainties), and 4) Funding decision. The data were used to address the above objectives by deploying a variety of techniques including: (i) Cohen’s k-scores to measure inter-rater agreement of countries on the uptake of MEAs as part of their funding decisions, (ii) a binary and multinomial logit model to analyse the role and weight of different HTA decision-making variables in determining the uptake and the type of MEA implemented respectively, and (iii) a binary logit model to capture the probability of a previously negative funding decision being reversed to positive following resubmission with a MEA and a gamma generalised linear model to capture the association between time to final funding decision and the presence of a MEA. 
Results: Poor to moderate agreement existed between countries (−0.29 &lt; κ &lt; 0.33) on their MEA utilisation for cancer medicines. MEA uptake was influenced by (i) uncertainties around cost-effectiveness, (ii) uncertainties around the utilities included in the economic model and (iii) the SVJ of innovation. Outcomes-based MEAs were driven by uncertainties around generalisability to clinical practice, and clinical benefit/ evidence, whereas financial MEAs by the SVJs of innovation and societal impact of the technology appraised. Previously rejected 7 medicines were significantly more likely to receive a favourable funding decision following a resubmission with a MEA, although approval with an outcomes-based MEA significantly increased the timing to final funding decision. 
Conclusions and policy implications: As MEAs are increasingly implemented across countries worldwide, the findings and policy implications arising from this thesis are critical in judging the true impact and sustainability of these agreements. First, identifying the aspects that shape the concept of “value” in decision-making under uncertainty can be used to optimise the respective MEA mechanisms used to address uncertainty, through informing transparent, “best-practice” guidelines for the design of more streamlined submission, negotiation and implementation processes for MEAs. Second, evaluation of whether previously implemented MEAs have met their objectives, is necessary in understanding how future agreements can be applied optimally to deliver the expected impact. If implemented appropriately, MEAs can play a key role in increased and faster access to new medicines. Future research can study the added value for patients and healthcare systems of the interventions approved with MEAs compared to other available interventions.