Glycan-binding proteins are commonly used as analytical reagents to detect the levels of specific glycan structures in biological samples. A detailed knowledge of the specificities of glycan-binding proteins is required for properly interpreting their binding data. A powerful technology for characterizing glycan-binding specificity is the glycan array. However, the interpretation of glycan-array data can be difficult due to the complex fine specificities of certain glycan-binding proteins. We developed a systematic approach, called outlier-motif analysis, for extracting fine-specificity information from glycan-array data, and we applied the method to the study of four commonly used lectins: two mannose binders (concanavalin A and Lens culinaris) and two galactose binders (Bauhinia purpurea and peanut agglutinin). The study confirmed the known, primary specificity of each lectin and also revealed new insights into their binding preferences. Lens culinaris's main specificity may be non-terminal, α-linked mannose with a single linkage at its 2' carbon, which is more restricted than previous definitions. We found broader specificity for bauhinea purpurea (BPL) than previously reported, showing that BPL can bind terminal N-acetylgalactosamine (GalNAc) and penultimate β-linked galactose under certain limitations. Peanut agglutinin may bind terminal Galβ1,3Gal, a glycolipid motif, in addition to terminal Galβ1,3GalNAc, a common O-linked glycoprotein motif. These results could be used to more accurately interpret data obtained using these well-studied lectins. Furthermore, this study demonstrates a systematic and general approach for extracting fine-specificity information from glycan-array data.

British Columbia listing decisions for 74% of the drugs reviewed by CADTH. Ontario agreed with CADTH for 76% of the drugs. Positive CADTH recommendations in particular often translated to availability in British Columbia and Ontario. Of the 57 drugs that received positive CADTH recommendations, 82% (47) are available in BC and 93% (53) are available in Ontario. Of the 36 drugs receiving negative CADTH recommendations, 61% (22) are unavailable in BC and 50% (18) are unavailable in Ontario. ConClusions: A positive CADTH recommendation is a good predictor of drug availability in British Columbia and Ontario. A drug that receives a negative CADTH recommendation, however, still has a significant probability of being listed by each province's health care system, especially through their special access programs. HC2

ReseaRch Podium PResentations-session i studies on hta agencies ag1 the geRman nice oR the geRman nasty? an analysis of iqwig decisions and RequiRements foR an 'added benefit'

A365for the FDA, EMA, Health Canada and Australia the Australian Therapeutic Goods Administration. The studies used to make regulatory decisions were then compared to the studies used in the reimbursement decisions of France, Scotland, Canada and Australia. Results: In all 15 cases reviewed the FDA, EMA and Health Canada used at least one of the same studies to come to their decision and in 13 of the cases Australia also used that same study. In 14 cases the FDA approved the drug before the other regulatory authorities; the longest time before another regulatory agency approved a drug was 15 months for rilpivirine. In six cases the FDA commissioned studies that other regulatory bodies and reimbursement agencies used later. All of the studies were interventional studies. Reimbursement agencies always used studies that were previously cited in regulatory documents. These agencies would also use studies intended for the regulatory approval of another drug as a source for information in a review. ConClusions: Reimbursement agencies and other regulatory agencies are influenced by the FDA in the studies they consider, as illustrated by at least six cases in which other agencies used studies commissioned by the FDA after approval. This influence is easier to see in the last five years, but may be older than that due to improvements in published reports.

IntroductionThe relationship between heath technology assessment (HTA) recommendations and drug prices has received little attention in the published literature. We consider whether target population sizes estimated as part of positive HTA decisions impact future price changes. We hypothesize that larger target populations may result in larger drug price reductions, as overall budget impact is an important component of price negotiations.MethodsHTA and pricing data were obtained from the Context Matters Market Access Platform (MAP) and IHS Markit's PharmOnline International (POLI) pricing database, respectively. We analyzed 55 HTA decisions from the Gemeinsame Bundesausschuss (G-BA; Germany) and the Haute Autorité de Santé (HAS; France) for oncology products receiving European Medicines Agency approval between 2011 and the end of 2014. Pricing and HTA histories were tracked from the beginning of 2012 until October 2018. Using multiple regression to control for HTA agency, country-specific scores (Improvement in Actual Benefit and Additional Benefit scores), pack size, and initial price, we examined the relationship between a drug's price change in the year following an HTA review and the increase in target population resulting from the HTA decision.ResultsWe found that larger increases in target population were related to larger reductions in drug prices (p = 0.014). The magnitude of the effect size was low.ConclusionsFor the sample evaluated, we found a small but statistically significant association between target population size increases (as estimated by HTA bodies) and price reductions, supporting our hypothesis that target population plays a role in price negotiations. Confidential discounts and managed-access agreements likely account, in part, for the low magnitude of the observed association. Future work on this topic will involve larger samples covering a greater number of HTA agencies to improve the power and generalizability of the analysis.