Systematic review of real-world studies evaluating the impact of medication non-adherence to endocrine therapies on hard clinical endpoints in patients with non-metastatic breast cancer.

Breast cancer, one of the most common malignancies, is associated with significant economic and health burden both at the patient and societal level. Although medication non-adherence to endocrine breast cancer therapies is common, so far only limited systematic evidence has been available on its quantitative consequences, as previous systematic reviews focused mainly on factors contributing to medication non-adherence. The objective of this review was to explore the implications of medication non-adherence to endocrine therapies on hard clinical outcomes in breast cancer based on real-world studies. A systematic literature review was conducted on PubMed; empirical evidence on hard clinical endpoints (i.e., survival, disease-free survival, metastasis and recurrence) were extracted from uni- or multivariate statistical analyses from retrospective or prospective cohort studies. Of the 2,360 identified records, 12 studies met the inclusion criteria. Two studies identified significant positive association between medication non-adherence and the risk of distant metastasis, three articles between medication non-adherence and the recurrence of breast cancer, two studies between medication non-adherence- and non-persistence and of worse disease-free survival and eight articles between medication non-adherence and mortality. There was only one study where the positive association between medication adherence and survival did not apply to all subgroups. The strong evidence on the negative health consequences of non-adherence to breast cancer treatments indicates the need for the regular monitoring of medication adherence. Furthermore, explicit inclusion of adherence enhancing interventions into health policy agenda would be warranted to improve medication adherence also at a system level.

Identifying Patient Access Barriers for Tumor Necrosis Factor Alpha Inhibitor Treatments in Rheumatoid Arthritis in Five Central Eastern European Countries.

INTRODUCTION: Although there is a significant utilization gap of biologic medicines in the EU, many studies estimate equity in patient access to biopharmaceuticals only based on their availability on the national list of reimbursed medicines. Hidden access barriers may facilitate financial sustainability of pharmaceuticals in less affluent EU countries; however, they have rarely been documented in scientific publications. Our objective was to explore these access barriers for tumor necrosis factor (TNF) alpha inhibitors in rheumatoid arthritis (RA) in five Central and Eastern European countries. METHODS: A detailed interview guide was developed based on multi-stakeholder workshops and a targeted literature review. In each participant country 3-3-3-3 interviews with payers, rheumatologists, patients/patient representatives, and industry representatives were conducted. Responses were aggregated at a country level and validated by primary investigators in each country. RESULTS: Limited number of RA centers and consequently significant travelling time and cost for patients in distant geographical areas, uneven budget allocation among centers, limited capacity of nurses, narrowed patient population in national financial protocols compared to international clinical guidelines in initiating or continuing biologics, high administrative burden in prescribing biologics and limited health literacy of patients were the most relevant barriers to timely patient access in at least three participant countries. CONCLUSION: Assessing only the availability of TNF alpha inhibitors on the national list of reimbursed medicines provides limited information about real-world patient access to these medicines. Revealing hidden access barriers may contribute to initiate policy actions which could reduce inequity in patient access.

Barriers and facilitators of exploiting the potential of value-added medicines.

INTRODUCTION: Pharmaceutical research and development (R&D) is costly and only a minority of patients can access innovative medicines due to affordability constraints. Value-added medicines (VAMs) can offer potential benefits at significantly lower R&D costs. AREAS COVERED: VAMs may address different health care needs and problems, including off-label use of medicines, poor patient adherence, problems related to polypharmacy, need for home and/or personalized health care services. However, several barriers prevent societies from maximizing the benefits of incremental innovation related to VAMs. Generic manufacturers have limited budget and experience to demonstrate the value of new VAMs. Current market exclusivity options do not efficiently exclude freeridership and do not guarantee a return on investment for VAM innovators. Value propositions of VAMs are limitedly consistent with current HTA frameworks, consequently, incremental innovation is not acknowledged, nor rewarded with differential pricing by payers. Moreover, VAMs are often perceived solely as generic medicines by prescribers. EXPERT OPINION: Current practices may need to be reconsidered to exploit the full societal benefit of VAMs, including more efficient policies to guarantee market exclusivity for incremental innovation, acknowledgment of a fair price premium based on a specific value framework and the acceptance of low-cost evidence generation methods.

Behind the subcutaneous trastuzumab hype: evaluation of benefits and their transferability to Central Eastern European countries.

INTRODUCTION: Trastuzumab, the standard treatment for HER-2 positive breast cancer, may be associated with access restrictions in countries with severe economic constraints. This study aimed to compare intravenous (IVT) and subcutaneous trastuzumab (SCT) forms and to explore the transferability of value propositions to Central and Eastern European (CEE) countries. Areas covered: After screening 376 abstracts, 42 articles were included in the final review. Statistical test results were rarely reported; therefore, the similarity of adverse event profiles of SCT and IVT could not be validated. Potential time savings for patients due to subcutaneous administration was not validated in CEE settings, where patient's waiting time for treatment administration is fairly long. Standard patient reported outcome instruments were rarely used to confirm the preference of patients/health care professionals to SCT over IVT. Moreover, feasibility of self/home administration of SCT, especially in case of concomitant intravenous chemotherapies, was not considered. Cost comparisons considered neither the patent expiry of IVT nor the incremental cost of potential differences in adverse events. Expert commentary: Potential benefits of SCT were not tested by any studies in CEE countries. The main policy objective should be to facilitate the uptake of multisource biologicals in lower income countries with access barriers.

Overview on Patient Centricity in Cancer Care.

Successful implementation of treatment in cancer care partially depends on how patients' perspectives are taken into account, as preferences of health care professionals and patients may differ. Objectives of this exploratory research were (I) to identify patient preferences and values (PPVs) in cancer care as indicated by patient organizations (POs), (II) to determine how these PPVs are captured in cancer care guidelines and (III) to review how guidelines take into account these PPVs. Based on a survey developed and completed by 19 POs, a literature review was conducted to analyse how patient perspectives are incorporated in oncology treatment guidelines. Based on survey results traditional health technology assessment value propositions of oncology care, such as extended life, treatment-free remission and pain reduction, were also highly rated by POs. However, the heterogeneity of cancer PPVs were clearly reflected in the survey results. PPVs in cancer care guidelines were mostly limited to those micro-level aspects that are strictly related to health care provision, such as side-effects and comorbidities. Patient experience, emotional support and convenience of care were relatively neglected fields in the reviewed guidelines. Patient engagement was rarely presented in the guideline development phase. POs believe that patients should be encouraged to take an active role in their own care due to the heterogeneity of cancer patients and PPVs. Even if patient-centricity is a leading paradigm in cancer policy, based on our research it is not yet standard practice to include patients or POs at all appropriate levels of decision-making processes that are related to their health and well-being. Patient engagement should be an integral part of cancer care decision-making. This complexity must be reflected throughout policy making, avoiding a population level "one-size-fits-all" solution.

Is there a reason for concern or is it just hype? - A systematic literature review of the clinical consequences of switching from originator biologics to biosimilars.

INTRODUCTION: While prescribing biosimilars to patients naive to a biologic treatment is a well-accepted practice, switching clinically stable patients from an originator to a biosimilar is an issue for clinicians. Well-designed clinical trials and real-world data which study the consequences of switching from an originator biologic treatment to its biosimilar alternative are limited, especially for monoclonal antibodies. Areas covered: A systematic literature review was conducted on PubMed to identify evidence of the consequences of switching from original biologics to biosimilars. References of included papers were also scrutinized. After a title-, abstract- and full text screening, out of the 153 original hits and 77 additional ones from screening the references, 58 papers (12 empirical papers, 5 systematic reviews and 41 non-empirical papers) were included. Expert opinion: Preventing patients on biologic medicines from switching to biosimilars due to anticipated risks seems to be disproportional compared to the expected cost savings and/or improved patient access. Indeed, it is the opinion of the authors that the concern of switching to biosimilars is overhyped.

Prognosis, Cost, and Occurrence of Colorectal, Lung, Breast, and Prostate Cancer in Hungary.

BACKGROUND: There is an increasing social debate on expenditures on the care of patients with malignant diseases, especially in Central Eastern European countries with limited health resources. OBJECTIVES: The aim of this research was to estimate the epidemiological and quality measures and resource use indicators in Hungary in four malignant conditions (breast, colorectal, lung, and prostate cancer) from the National Health Insurance Fund (NHIF) database. METHODS: Survival and cost analyses were performed on the NHIF database. Patient records containing the International Classification of Diseases (ICD) codes C50 (breast cancer), C18-C20 (colorectal cancer), C33-C34 (lung cancer), and C61 (prostate cancer) were considered eligible. Inclusion criteria were at least two consecutive ICD codes between 2000 and 2012, with a minimum of 30-day difference, or one ICD code, followed by patient death within 60 days. A total of 428,860 social insurance numbers met inclusion criteria. RESULTS: The number of new cases was 6381 for breast cancer, 8457 for colorectal cancer, 8902 for lung cancer, and 3419 for prostate cancer. The probability of 5-year overall survival from the first diagnosis was 75.2%, 41.3%, 17.1%, and 62.1%, respectively. Median time from first diagnosis to treatment initiation was less than 1 month in all conditions except for lung cancer. The annual cost of treatment was €2585, €3165, €4157, and €2834, respectively. Cost figures were compared with hemophilia as benchmark (€8284). CONCLUSIONS: The results indicated that the database of the Hungarian NHIF is suitable for real-world data analysis in the field of oncology and can support long-term evidence-based policymaking.

Factors associated with medication adherence in patients with chronic obstructive pulmonary disease.

BACKGROUND: Predictors of medication adherence are not well known in chronic obstructive pulmonary disease (COPD). It is therefore necessary to identify factors associated with adherence to improve the effectiveness of COPD management within real-world situations. OBJECTIVES: The goals of this study were to estimate adherence to respiratory medication and to identify factors related to adherence in COPD patients. METHODS: This was an observational, cross-sectional study conducted on a sample of COPD outpatients. The following information was obtained: adherence to respiratory therapy (Morisky Medication Adherence Scale), age, gender, smoking status, COPD severity [Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage], lung function [post-bronchodilator forced expiratory volume in 1 s (FEV(1))], treatment regimen for COPD, COPD medication costs per month paid by the patient and health-related quality of life (EuroQol 5-dimension questionnaire). A multivariate logistic regression analysis was performed to identify the independent predictors of adherence. RESULTS: Of the 170 participants (mean age 63.8 years, 41.8% male), 58.2% reported optimal adherence. Adherence to respiratory therapy was associated with age, current smoking status, number of respiratory drugs, number of daily respiratory drug doses and quality of life (p < 0.005). Adherence to respiratory therapy was not related to gender, GOLD stage, FEV(1) or COPD medication costs. CONCLUSIONS: Adherence to COPD medication regimens is poor. Less frequent dosing regimens could be an effective method to enhance adherence to respiratory therapy. Quality-of-life monitoring within clinical practice settings could facilitate improved medication adherence.