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Introduction: utcome-based agreements (OBAs) are occasionally deployed to relieve the burden of high drug prices on healthcare budgets. However, it is not clear when manufacturers are willing to collaborate in establishing such agreements. Therefore, we explored the feasibility of OBAs from the manufacturer’s point of view. Methods: Dutch market-access experts from eight major pharmaceutical companies, globally active in the field of oncology, were interviewed. Opinions were compiled, and interviewees and their colleagues were then given the chance to review the manuscript for additional comments. Results: Most interviewees believe that OBAs can be useful in providing access to off-label use of authorised medicines, especially when no alternative treatment is available for seriously ill patients. For the licenced indications, manufacturers seem to be more inclined to collaborate when there is a potential incentive to improve market-access (e.g., if the product is not used because of concerns regarding its effectiveness). However, manufacturers are less likely to collaborate when there are greater financial risks for the company. Further concerns were definition of outcome or performance, the impact of compliance on the effectiveness of a drug, administrative burden, uncertainty regarding revenue recognition and the challenges of reimbursing combination therapies. Discussion: Market-access interviewees were generally positive about OBAs, however they were more reluctant towards OBAs for registered indications with low response-rate. The definition of performance or outcome and its clinical relevance and validity, the feasibility of OBAs and their administrative burden are relevant aspects that need to be addressed in advance. Ideally, countries should collaborate to share the outline of OBAs and create shared databases to accumulate evidence.

Background: Capecitabine is a widely prescribed oral anticancer agent. We studied medication adherence and explored its use in daily practice from a patients’ perspective. Methods: Patients (n=92) starting capecitabine were followed up to five 3-week cycles. Adherence was assessed using a pill count, pharmacy data and dosing information from the patients’ medical file. Self-reported adherence was measured using the Medication Adherence Report Scale (MARS). At baseline and during week 2 of cycles 1, 3 and 5, patients filled out questionnaires about quality of life, symptoms, attitude towards medicines and disease and use in daily practice. Simultaneously, blood samples were taken to determine the area under the curve (AUC) of 5’-deoxy-5-fluorouridine (5’-DFUR), 5-fluorouracil (5-FU) and α-fluoro-β-alanine (FBAL) by a population pharmacokinetic model. Associations between AUCs and patient-reported symptoms were tested for cycles 3 and 5.Results: Most patients (84/92; 91%) had an adherence rate of ≥95% and ≤105%. The percentage of patients reporting any non-adherence behaviour measured with MARS increased from 16% at cycle 1 to 29% at cycle 5. Symptoms were reported frequently and the dosing regimen was adjusted by the physician at least once in 62% of patients. In multivariate analysis the probability of an adjustment increased with the number of co-medication (OR 1.19, 95%CI:1.03-1.39) and a stronger emotional response to the disease (OR 1.32, 95%CI:1.10-1.59)..The AUC of 5’-DFUR was associated with weight loss (OR 1.10, 95%CI:1.01-1.19), AUC of FBAL with hand-foot syndrome (OR 0.90, 95%CI:0.83-0.99), rhinorrhea (OR 1.21, 95%CI:1.03-1.42 weight loss (OR 1.09, 95%CI:1.00-1.20) and depression (OR 0.90, 95%CI:0.82-0.99). Side effects were reported by one third of patients as the reason to discontinue treatment.Conclusion: Adherence to capecitabine was generally high. Nevertheless, adherence measured with MARS decreased over time Adherence management to support implementation of correct capecitabine use is specifically relevant in longer term treatment. In addition, it appears that adverse event management is important to support persistence. With the extending armamentarium of oral targeted anticancer agents and prolonged treatment duration, we expect the issue of medication adherence of increasing importance in oncology.