Background: Health technology assessment (HTA) plays an important role in reimbursement decision making in Poland and its principles are similar to those used in other countries. However, specific inter-country differences, such as substantial divergence in budgetary resources, may lead to variation in actual HTA practices, e.g. in the approach to uncertainty. Cancer drug reimbursement is a decision-taking area associated with substantial uncertainty. One of its important sources is the presence of crossover (treatment switching) in clinical trials. Objectives: To review the appraisal processes completed for cancer drugs by the Polish HTA agency (AOTMiT) and to compare AOTMiT to the British, Australian and Canadian HTA bodies with respect to strategies of addressing crossover-related uncertainty. Methods: Cancer drug assessment processes in AOTMiT, where a substantial crossover took place were reviewed and subsequently matched with the assessments conducted by NICE, PBAC and pCODR. Ways to approach the crossover-related uncertainty, the influence of uncertainty on the recommendation and uncertainty management strategies were examined. Results: 29 HTA processes related to 6 drugs were included. The crossover rate ranged from 51% to 85% and ITT analyses did not show statistically significant survival benefit. AOTMiT more often yielded negative recommendation, showed less consistent approach to crossover-related uncertainty and a narrower scope of adopted uncertainty management strategies. Conclusions: Crossover constitutes a vital source of uncertainty in the assessments of new cancer therapies. The lack of consistent standards decreases the transparency of assessment processes and can contribute to undertaking suboptimal reimbursement decisions.

Introduction. The BRAF V600E mutation (BRAFmt) occurring in the metastatic colorectal cancer (mCRC) patients is associated with poorer prognosis, in comparison to the wild-type variant of the BRAF gene (BRAFwt). Aim of this work was to assess the clinical efficacy of bevacizumab (BEVA) or standard chemotherapy (ChT) in the 2 nd or further lines of treatment in mCRC BRAFmt population. Material and methods. MEDLINE/PubMed, Embase and Cochrane CENTRAL databases were systematically searched. The reference lists of relevant studies were also checked. Results. 6 eligible trials were identified: MOMA (BEVA ± ChT), allowing for limited overall survival (OS) assessment, WJOG 6210G (BEVA + FOLFIRI), RAISE and 20050181 (FOLFIRI), PICCOLO and Spindler 2013 (irinotecan monotherapy). None of those trials were designed for the treatment evaluation in BRAFmt population. Available evidence was restricted to limited analyses in small subgroups (from a few to several dozens of patients), occasionally comprising RAS gene mutation (RASmt) as well. Based on the identified studies, the comparison of BEVA ± ChT vs. ChT or among different ChTs in BRAFmt population was not feasible.In case of BEVA (MOMA), OS hazard ratio (HR) for BRAFmt vs. BRAFwt was 1.52 (95% CI: 0.79-2.89) with difference in medians equal to 12.1 months (19.2 vs. 31.3 months, respectivelly), and BRAFmt or RASmt patients had median OS lower by 7.9 months and median progression free survival (PFS) by 3.0 months in WJOG 6210G trial. In case of ChT, median PFS was lower in BRAFmt by 12-67% (HRs range: 1.01-5.3), and median OS by 34-73% (HRs range: 1.05-5.00).Conclusions. Due to limited clinical evidence, assessment of further lines of treatment in BRAFmt mCRC patients is uncertain, however existing data consistently suggest lower effectiveness of BEVA ± ChT or ChT in BRAFmt, than in BRAFwt subgroup. Hopefully, combining anti-EGFR therapies with BRAF/MEK inhibitor is expected to improve prognosis of those patients.

Idiopathic pulmonary fibrosis (IPF) is a rare disease characterised by age-dependent incidence, unclear aetiology and progressive course. Given the complexity of the diagnostic pathway and limited therapeutic options, and according to the fact that the Polish society is ageing, healthcare and social security expenditure are considerable and likely to rise. Until recently, there was no effective treatment for patients with IPF. After diagnosis only procedures that relieve the symptoms of the disease and treat its complications or lung transplantation were offered. In recent years a huge interest in this clinical entity has been seen. This resulted in the introduction of new drugs, whose efficacy has been confirmed in reliable clinical trials and whose slow the progression of the disease and improve survival of patients. The first such drug was pirfenidone; however such treatment is not available in Poland. Furthermore, due to the inadequacy of Polish legislative reimbursement solutions, which do not take into account the specific nature of rare disease, there are not used any favourable solution during the assessment of public funding of orphan drugs. This is contrary to European consensuses on an egalitarian approach to the use of orphan drugs. It is necessary to develop standards of care for IPF patients, including systemic solutions and the inclusion of the drugs used in the treatment of IPF on the reimbursement list. In long term this will reduce the financial burden associated with the disease, and thus reduce the direct and indirect costs resulting from its prevalence.

or cisplatin, as well as doublets of oxaliplatin with fluoropiridine (classified as less effective). According to LMoH the following chemotherapeutics were reimbursed in the treatment of adenocarcinomas of pancreas: carboplatin, cisplatin, cyclophosphamide, dacarbazine, doxorubicin, etoposide, fluorouracil, gemcitabine, ifosfamide, irinotecan, mitomicin, oxaliplatin, vinblastine, vincristine and vinorelbine. Database of Polish public payer showed that from 2013 to 2015 (as for first half of the year) 1138 patients with the mentioned malignancies were treated with reimbursed drugs and gemcitabine was used in a great majority of them (n= 923). Among less commonly utilized drugs were fluorouracil (n= 224), oxaliplatin (n= 189) and cisplatin (n= 125). Other were administered to single patients (irinotecan n= 23, etoposide n= 11, carboplatin, vinorelbine n= 4 each, doxorubicin n= 3, cyclophosphamide, vinblastine and vinorelbine n= 1 each). There were also 20 patients from 2014 to 2015 treated with nab-paclitaxel reimbursed outside standard fashion (i.e. outside LMoH). ConClusions: There is a strong adherence of recommended, reimbursed and actually used drugs in pancreatic adenocarcinoma if it comes to gemcitabine, fluorouracil, oxaliplatin and cisplatin in Poland.