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Deterministic sensitivity analyses (DSA) remain important to interpret the effect of uncertainties in individual parameters on results of cost-effectiveness analyses. Classic DSA methodologies may lead to wrong conclusions due to a lack of or misleading information regarding marginal effects, non-linearity, likelihood and correlations. In addition, tornado diagrams are misleading in some situations. Recent advances in DSA methods have the potential to provide decision makers with more reliable information regarding the effects of uncertainties in individual parameters. This practical application discusses advances to classic DSA methods and their implications. Three methods are discussed: stepwise DSA, distributional DSA and probabilistic DSA. For each method, the technical specifications, options for presenting results, and its implications for decision making are discussed. Options for visualizing DSA results in incremental cost-effectiveness ratios and in incremental net benefits are presented. The use of stepwise DSA increases interpretability of marginal effects and non-linearities in the model, which is especially relevant when arbitrary ranges are implemented. Using the probability distribution of each parameter in distributional DSA provides insight on the likelihood of model outcomes while probabilistic DSA also includes the effects of correlations between parameters. Probabilistic DSA, preferably expressed in incremental net benefit, is the most appropriate method for providing insight on the effect of uncertainty in individual parameters on the estimate of cost effectiveness. However, the opportunities provided by probabilistic DSA may not always be needed for decision making. Other DSA methods, in particular distributional DSA, can sometimes be sufficient depending on model features. Decision makers must determine to which extent they will accept and implement these new and improved DSA methodologies and adjust guidelines accordingly.

Last years, more than 46 unique biosimilars were approved by EMA and/or US-FDA following patent expiration of reference products. Biosimilars are not identical like generics, but highly similar versions where demonstrating biosimilarity of quality attributes (QAs) to a reference product is the basis of development and regulatory approval. Information on QAs assessed to establish biosimilarity may not always be publicly available, although this information is imperative to understand better the science behind biosimilars approval. This study aims to identify QA types reported in publications presenting biosimilarity assessments of (intended) biosimilars over time. English full-text publications presenting biosimilarity assessments of QAs for (intended) biosimilars between 2000 and 2019 identified from PubMed and EMBASE. Publication characteristics and QAs classified into: structural (physicochemical properties, primary structure, higher-order structures (HOSs), post-translational modifications (PTMs), and purity and impurities) and functional (biological and immunochemical activities) were extracted from publications. Seventy-nine publications were identified (79% open-access, 75% industry-sponsored, 62% including unapproved biosimilars, and 66% involving antibodies). Reporting frequencies varied for QA types: biological activity (94%), physicochemical properties (81%), PTMs (79%), primary structure (77%) purity and impurities (73%), HOSs (58%), and immunochemical activity (41%). The number of publications increased from 6 (7%) during 2009–2011 to 62 (79%) during 2015–2019. Eighteen (28%) publications reported all QA types relevant to an active-biological-substance. Reporting of most QA types increased over time that most evidenced by immunochemical activity (from 0% to 47%) which occured after EMA monoclonal

Objectives: The objective of this study was to construct an early economic evaluation for acalabrutinib for relapsed chronic lymphocytic leukaemia (CLL) to assist early reimbursement decision making. Scenarios were assessed to find the relative impact of critical parameters on incremental costs and quality-adjusted life-years (QALYs). Methods: A partitioned survival model was constructed comparing acalabrutinib and ibrutinib from a UK national health service perspective. This model included states for progression-free survival (PFS), post-progression survival (PPS) and death. PFS and overall survival (OS) were parametrically extrapolated from ibrutinib publications and a preliminary hazard ratio based on phase I/II data was applied for acalabrutinib. Deterministic and probabilistic sensitivity analyses were performed, and 1296 scenarios were assessed. Results: The base-case incr

INTRODUCTION – Drug rediscovery (DR) provides opportunities for new treatments and patient benefit. However, due to the barriers and the lack of an incentive in the rediscovery process, DR often does not lead to an extension of indications or market authorization. Hence, the patient does not have access to the rediscovered drug, or only off-label with possible safety issues involved. On the other hand, cases of DR that did register and now benefit from regulatory exclusivity are also part of a public debate as there is a perception of low efforts and high prices asked. For a balanced discussion on this topic, it is important to have better insights in the landscape of DR. This will support policymakers to improve the conditions for DR with patient benefit as a focus. AIM: To examine the efforts needed and barriers of different routes to get drug rediscovery to the patient. METHODS – 29 experts from different actors were interviewed about specific costs and barriers of DR through one of the following routes: registration, delivered compounding, magistral formulas or off-label use. RESULTS – Costs of DR fluctuate heavily between projects and routes and must be seen as indicative. Costs of off-label use are almost nihil, while the development of the production of magistral formulas and delivered compounding could reach up to € 10.000 and € 25.000, respectively. Registration of rediscovered drugs is found most expensive, ranging from € 300.000, if no clinical research is needed, to several millions of euros if additional clinical studies are required. One of the barriers to drug rediscovery is the lack of a business case for DR due to the inability to ask a higher price than a generic already on the market. Another barrier is that medical professionals do not value the registration of DR and do not see registration as a necessary goal of DR. CONCLUSIONS – Paying a fair price for DR is essential for sustainable DR activities and the status-quo causes therapeutic chances