Access to novel cancer medicines in four countries in Central and Eastern Europe in relation to clinical benefit.

BACKGROUND: Almost 100 novel cancer medicines have been approved in Europe over the last decade. Limited public health care resources in countries in Central and Eastern Europe (CEE) call for a prioritization of access to effective medicines. We investigated how both reimbursement status and waiting time to reimbursement correlate with the magnitude of clinical benefit provided by novel medicines in four selected countries (Czechia, Hungary, Poland, and Slovakia). MATERIALS AND METHODS: A total of 124 indications of 51 cancer medicines with marketing authorization by the European Medicines Agency in 2011-2020 were included and followed up until 2022. Data on reimbursement status and waiting time to reimbursement (i.e. time from marketing authorization to national reimbursement approval) were collected for each country. Data were analyzed in relation to clinical benefit status (i.e. substantial versus nonsubstantial clinical benefit) of indications according to the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). RESULTS: The degree of reimbursement differed between countries with 64% of indications with reimbursement in Czechia, 40% in Hungary, 51% in Poland, and 19% in Slovakia. In all countries, a significantly greater proportion of indications with a substantial clinical benefit was reimbursed (P < 0.05). The median waiting time to reimbursement ranged from 27 months in Poland to 37 months in Hungary. No significant differences in waiting time in relation to clinical benefit were observed in any country (P = 0.25-0.84). CONCLUSIONS: Cancer medicines with a substantial clinical benefit are more likely to be reimbursed in all four CEE countries. Waiting times to reimbursement are equally long for medicines with or without a substantial clinical benefit, indicating a lack of prioritization of fast access to medicines delivering a substantial benefit. Incorporation of the ESMO-MCBS in reimbursement assessments and decisions could aid in better utilization of limited resources to deliver more effective cancer care.

The quality of life following allogeneic hematopoietic stem cell transplantation - a multicenter retrospective study.

UNLABELLED: Although allogeneic haematopoietic stem cell transplantation (allo-HSCT) offers a unique curative potential, it may be connected with high treatment-related morbidity and mortality. Besides many organ complications, allo-HSCT may significantly affect quality of life (QOL). PATIENTS AND METHODS: Between January 2011 and December 2012, five hundred and ninety patients (pts) from 6 transplant centers in the Czech Republic filled in the questionnaire for the quantitative measurement of QOL using Functional Assessment of Cancer Therapy-General (FACT-G) version 4. Study cohort characteristics were as follows: 325 males, 340 pts received myeloablative conditioning, 383 pts received PBPC, representation of diagnoses; acute leukemia (n=270), bone marrow failure (n=36), chronic myeloid leukemia (n=74), myelodysplastic/myeloproliferative syndrom (n=110), lymphoproliferative disease (n=93). The median age at allo-HSCT was 43 years (range: 1.7 - 71.0), the median time from allo-HSCT to questionnaire completing was 3.8 years (range: - 0.2 - 21.6). The earliest allo-HSCT was performed in November 1989, the last in September 2012. In this retrospective study, we investigated the impact of various factors on the QOL after allo-HSCT: age, gender, diagnosis, type of conditioning, time from diagnosis to allo-HSCT, disease stage, graft type, donor type, time from allo-HSCT to questionnaire completing, GVHD, relapse. Only data from patients who were more than 3 months after allo-HSCT were used for the multivariate analysis. The overall results of the total FACT-G score (median=85.0; range: 29-108) as well as the results of each specific dimension - PWB (median=23.0; range: 5-28), SWB (median=24.0; range: 7-28), EWB (median= 19.0; range: 4-24), FWB (mean=21.0; range: 2-28) showed a value in the highest quartile of the possible evaluation. In multivariate analysis, an inferior QOL score was reported for patients with aGVHD (p=0.002), cGVHD (p<0.001), QOL decreased with increasing age (p=0.048) and increased with time elapsed since allo-HSCT (p<0.001).Allogeneic HSCT represents an important intervention into the overall integrity of the organism. In particular, the development of GVHD can cause very serious organ, but also mental problems which can significantly reduce the QOL. The QOL is steadily increasing with increasing interval from allo-HSCT but improvement and disappearance of these complications may take many years, and sometimes these effects may probably persist permanently.

Transferability of National Institute for Health and Clinical Excellence recommendations for pharmaceutical therapies in oncology to Central-Eastern European countries.

The health burden of malignancies is greater in Central-Eastern Europe than in Western Europe. Furthermore, these countries have more limited healthcare resources, and therefore transparent decision criteria for innovative cancer therapies, including the assessment of cost-effectiveness, are an absolute necessity. Transferability of good-quality technology assessment reports, especially those prepared by National Institute for Health and Clinical Excellence (NICE) in the UK, could be highly beneficial to prevent duplication of efforts and save resources for local technology assessment. Our objective was to summarise key factors influencing the transferability of NICE recommendations in oncology for policy makers and oncologists in Central-Eastern Europe without personal experience in health technology assessment. In general, NICE recommendations are not transferable without adjustment of the analyses to local data. Even if the recommendation is positive, the conclusion can still be negative in lower-income countries, mainly due to relative price differences and the significance of the local budget impact. Technologies with negative NICE recommendations can still be cost-effective in Central-Eastern Europe due to the worse health status and therefore the greater potential health gain of the targeted population. The appropriateness of reimbursement decisions must be improved in Central-Eastern Europe, but copying NICE recommendations without local adjustment may do more harm than good.

Occurrence of overactive bladder in patients with benign prostatic hyperplasia in the Czech Republic.

INTRODUCTION: Bladder outlet obstruction (BOO) due to prostatic hyperplasia is often accompanied by overactive bladder (OAB) symptoms, which often disappear after specific BOO pharmacotherapy. The aim of this study was to map out the spectrum in BOO pharmacotherapy to find out the occurrence of OAB in this population and to find its treatment. MATERIALS AND METHODS: Follow-up consists of a retrospective and a prospective part, which includes all the patient's data related to the lower urinary tract symptoms in BOO and OAB. In all, 654 data record forms were distributed during the study and 98% of those were validated. RESULTS: According to our observations, alpha-blockers were used most frequently at the beginning of BOO treatment (73%), followed by phytopharmaca (19.9%) and finally finasteride (5.5%). If the treatment is changed, the proportion of finasteride increases. Only a small number of patients with BOO and OAB are treated in combination with antimuscarinics. CONCLUSIONS: A combined therapy (alpha-blocker + antimuscarinics) is effective in a majority of men with infravesical obstruction and symptoms of OAB. However, OAB in our study was primarily underdiagnosed in almost 50% of all patients treated for LUTS.

Clinical outcomes and direct hospital costs of reduced-intensity allogeneic transplantation in chronic myeloid leukemia.

A reduced-intensity conditioning allogeneic stem cell transplantation was given to 19 patients (aged 15-59 years) in the first chronic phase and one patient in the accelerated phase with chronic myeloid leukemia (CML) after a regimen consisting of fludarabine (Flu), busulfan (Bu) and ATG Fresenius. The median follow-up was 27 months. Until day +100, no transplant-related mortality was recorded. The incidence of acute and chronic graft-versus-host disease (GvHD) was 55 and 75%, respectively. Two patients (10%) died from GvHD. Fourteen (70%) patients achieved molecular remission. Additional post-transplant intervention (donor lymphocyte infusion, imatinib) was necessary, however, in 10 patients (50% of the patients; non-achievement of stable molecular remission or later relapses). The total direct cost of the transplantation treatment for all of the patients came to 1,572,880 euro. If the patients had been treated with imatinib and followed-up with the same time period as they were following a transplantation, the direct cost of the imatinib treatment would have been 2,005,117 euro. The transplantation treatment appears to be less expensive after approximately 2 years of follow-up. Flu+Bu+ATG is a low-toxicity regimen for patients with CML. However, a close follow-up is necessary and about 50% of the patients require further therapeutic intervention.

[Review of the molecular genetics of the Lynch syndrome]. / Prehled molekulární genetiky Lynchova syndromu.

The molecular genetics of the hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) is reviewed. Recently, four genes (hMSH2, hMLH1, hPMS1, hPMS2) whose mutations are related to HNPCC were discovered. The products of these genes are homologues of the bacterial mismatch repair (MMR) system proteins MutS and MutL. Dysfunction of MMR system both in bacterial and human cells leads to the microsatellite instability (MI) in repetitive sequences of DNA. These sequences are also present in some tumor suppressor genes (e.g. TGF-beta RII or BAX). Therefore, the MI probably leads to the impairment of the cell cycle regulation and a carcinoma can develop from the clone of such cells with nonregulated growth.