Linking reimbursement to patient benefits for advanced therapy medicinal products and other high-cost innovations: Policy recommendations for outcomes-based agreements in Europe.

OBJECTIVES: Health technology assessment (HTA) of advanced therapy medicinal products (ATMPs), such as high-cost, one-time cell and gene therapies, is particularly challenging. Outcomes-based agreements (OBAs) are a potential solution to mitigate the risks while providing access to patients but are not widely used across Europe. This study aimed to develop policy recommendations to support the acceptability and implementation of OBAs in Europe. METHODS: A policy sandbox approach was used to engage with stakeholders and explore how HTA organisations can support reimbursement decisions regarding OBAs for ATMPs. A panel of 38 experts from across the European region was convened in two workshops, representing payers, HTA organisations, patients, registries, and an industry trade body. RESULTS: Policy recommendations were developed to support the appropriate consideration of OBAs for reimbursing highly uncertain technologies, such as ATMPs. If a positive HTA recommendation cannot be made at the proposed price, then a simple price discount reflecting the uncertainty is preferred over complex solutions like OBAs. If an OBA is pursued, it should be designed collaboratively with all stakeholders to understand data collection feasibility and minimise burden to patients and providers. Payers are encouraged to approach OBAs as a tool for informed decision-making, including a readiness to make negative reimbursement decisions based on unfavourable evidence. CONCLUSIONS: The study presents a policy framework for using OBAs in reimbursement decisions. OBAs must be carefully designed, focusing on appropriateness and the burden of implementation. The relevant authorities should be committed to making decisions in light of the resulting evidence.

Environmental impact assessment in health technology assessment: principles, approaches, and challenges.

To reduce harm to the environment resulting from the production, use, and disposal of health technologies, there are different options for how health technology assessment (HTA) agencies can consider environmental information. We identified four approaches that HTA agencies can use to take environmental information into account in healthcare decision making and the challenges associated with each approach. Republishing data that is in the public domain or has been submitted to an HTA agency we term the "information conduit" approach. Analyzing and presenting environmental data separately from established health economic analyses is described as "parallel evaluation." Integrating environmental impact into HTAs by identifying or creating new methods that allow clinical, financial, and environmental information to be combined in a single quantitative analysis is "integrated evaluation." Finally, evidence synthesis and analysis of health technologies that are not expected to improve health-related outcomes but claim to have relative environmental benefits are termed "environment-focused evaluation."

PD-L1 diagnostic tests: a systematic literature review of scoring algorithms and test-validation metrics.

BACKGROUND: The programmed death receptor 1 (PD-1) protein is a cell-surface receptor on certain lymphocytes that, with its ligand programmed death ligand 1 (PD-L1), helps to down-regulate immune responses. Many cancer types express PD-L1 and evade immune recognition via the PD-1/PD-L1 interaction. Precision therapies targeting the PD-1/PD-L1 pathway have the potential to improve response and thereby offer a novel treatment avenue to some patients with cancer. However, this new therapeutic approach requires reliable methods for identifying patients whose cancers are particularly likely to respond. Therefore, we conducted a systematic literature review assessing evidence on test validation and scoring algorithms for PD-L1 immunohistochemistry (IHC) tests that might be used to select potentially responsive patients with bladder/urothelial cell, lung, gastric, or ovarian cancers for immunotherapy treatment. METHODS AND RESULTS: To identify evidence on commercially available PD-L1 IHC assays, we systematically searched MEDLINE and Embase for relevant studies published between January 2010 and September 2016 and appraised abstracts from recent oncology conferences (January 2013 to November 2016). Publications that met the predefined inclusion criteria were extracted and key trends summarized. In total, 26 eligible primary studies were identified, all of which reported on the test validation metrics associated with PD-L1 IHC tests in lung cancer, most using immunohistochemistry testing. There was significant heterogeneity among the available tests for PD-L1. Specifically, no definitive cutoff for PD-L1 positivity was identifiable, with more than one threshold being reported for most antibodies. Studies also differed as to whether they evaluated tumor cells only or tumor cells and tumor-infiltrating immune cells. However, all of the tests developed and validated to support a therapeutic drug in the context of phase 2-3 clinical trials reported more than 90% inter-reader concordance. In contrast, other PD-L1 antibodies identified in the literature reported poorer concordance. CONCLUSIONS: Published validation metric data for PD-L1 tests are mainly focused on immunohistochemistry tests from studies in lung cancer. The variability in test cutoffs and standards for PD-L1 testing suggests that there is presently no standardized approach. This current variability may have implications for the uptake of precision treatments.