INTRODUCTION: Several comparative real-world effectiveness studies on direct oral anticoagulants (DOACs) have been conducted, but an overview of the available evidence remains to be developed, which could provide a better understanding of the value of DOACs relative to vitamin K antagonists (VKAs). Areas covered: A systematic literature review was conducted on the available real-world evidence (RWE) of three DOACs (rivaroxaban, dabigatran, and apixaban) compared with VKAs (e.g. warfarin), in patients with nonvalvular atrial fibrillation (NVAF).This systematic literature review included RWE published up to December 2016. Studies with > 50 patients reporting on incident and prevalent NVAF cases were included. The following databases were searched: Medline, Embase, and the Cochrane Library. Outcomes of interest included thromboembolic events, all-cause mortality, bleeding events, and nonpersistence. Of the 562 RWE DOACs articles retrieved, 49 presented results for rivaroxaban versus VKAs, 79 for dabigatran versus VKAs, and 18 for apixaban versus VKAs. Substantial heterogeneity was found across patient population, outcome definition, and follow-up period. Major bleeding, ischemic stroke, and intracranial hemorrhage were the most frequent outcomes analyzed. Expert commentary: Overall, the RWE studies were aligned with the Phase 3 trials. However, conflicting results were reported for several outcomes of interest.

BACKGROUND AND AIMS: Real-world data on treatment patterns in Japanese hyperlipidemia patients with diabetes mellitus (DM) or prior atherosclerotic cardiovascular diseases (ASCVD) are lacking. METHODS: This is a retrospective, longitudinal cohort analysis of administrative claims data (Japan Medical Data Center [JMDC] and Medical Data Vision [MDV] databases) for patients prescribed a new hyperlipidemia medication between 2014 and 2015. Patients were followed for >/=12 months. Outcomes included prescribing patterns, persistence (discontinuations), and adherence (proportion of days covered). RESULTS: Data were analyzed for 11,718 and 27,746 DM, and 4101 and 14,356 ASCVD patients from the JMDC and MDV databases, respectively. Among previously-untreated patients, index prescriptions were primarily for moderate statins in the DM (JMDC: 74.7%, MDV: 77.5%) and ASCVD (JMDC: 75.4%, MDV: 78.5%) sub-cohorts. Combinations were rarely prescribed (/=80% across most drug classes. CONCLUSIONS: Many Japanese hyperlipidemia patients with DM or ASCVD are prescribed single-agent lipid-lowering therapy. Use of intensive therapy is lower than expected, and is suggestive of under-treatment. The low persistence rates are concerning, and warrant further study.

Aims: Non-vitamin K antagonist oral anticoagulants (NOACs) and vitamin K antagonists (VKAs) are used to prevent stroke in patients with atrial fibrillation (AF). This paper aimed to evaluate the clinical efficacy and safety of NOACs when compared to VKAs by calculating the number needed to treat (NNT) at 2 years using incidence rates and hazard ratios (HRs) derived from a meta-analysis of studies conducted in real-world settings. Materials and methods: HRs were sourced from a published systematic literature review and a meta-analysis of real-world evidence on the use of NOACs vs VKAs. Rivaroxaban, dabigatran, and apixaban vs VKAs were investigated. The efficacy outcomes included: a composite of ischaemic stroke and systemic embolism (IS/SE), ischaemic stroke (IS), and all-cause mortality. The safety analysis assessed major bleeding and intracranial haemorrhage (ICH). Results: Superiority of NOACs vs VKAs was observed in 10/15 comparisons. Treating patients with rivaroxaban and dabigatran was associated with a reduced risk of IS and all-cause mortality compared to VKAs, with one death prevented every 22 and 32 patients, respectively, and one IS prevented every 206 and 166 patients, respectively. Rivaroxaban was significantly associated with a reduced risk of IS/SE compared to VKA (NNT: 107). No significant differences were observed between apixaban and VKAs. Dabigatran and apixaban were associated with a reduced risk of major bleeding compared to VKA (NNT: 59 and 38, respectively). No significant difference was observed between rivaroxaban and VKAs regarding major bleeding. Rivaroxaban, dabigatran, and apixaban were significantly associated with a reduced risk of ICH (NNT: 205, 115, and 108, respectively). Limitations: Heterogeneity in definitions of major bleeding across studies. Conclusions: The NNT calculation, when approached and interpreted properly, is a practical measure of the effectiveness of a treatment. The calculation based on HRs showed that NOACs are safe and effective alternatives to VKAs in real life.

OBJECTIVES: Real-world evidence (RWE) may provide good estimates of absolute event probabilities and costs in patients in actual clinical practice, but their use in decision-analytic models poses many challenges. A literature review based on a systematic search was conducted to summarize the limitations of using RWE in decision-analytic modeling reported in the literature but also to identify existing recommendations about real-world modeling. METHODS: A literature search was performed on Medline and Embase databases, as well as relevant websites. No restrictions in language or geographical scope were imposed. RESULTS: A total of 14 references were included. RWE is recognized as a valuable source of data for market access and reimbursement, and as a complement to clinical trial evidence for treatment pathways, resource use, long-term natural history, and effectiveness. The main limitations identified in the literature were: confounding bias, missing data, lack of accurate data related to drug exposure and outcomes, errors during the record-keeping process, protection of private data, and insufficient numbers of patients. Although most submission guidelines recognized the potential biases associated with RWE, guidance on the appropriate methods to deal with these biases, and approaches to review different relevant evidence to inform model development, were scarce. Several initiatives have attempted to provide guidance on the use of RWE in decision-modeling. CONCLUSIONS: RWE is likely to be particularly valuable for informing healthcare policy-makers when formulating appropriate treatment pathways, encouraging the optimal allocation of scarce resources, and improving aggregate patient outcomes. However, little guidance is available on the relative merits of using efficacy and/or effectiveness evidence in Health Technology Appraisal submissions. Further research is needed to better understand these methods and their potential applications in a broader range of scenarios and simulation studies, and their impact on economic modeling.

Rising budget constraints and demands for healthcare services create additional complexity within the decision process for resource allocation. Innovations and scientific progress have been shown to be key drivers of the increase in healthcare expenditures (1). In the context of rising medical care costs and limited resources, Health Technology Assessment (HTA) was developed as a tool to inform decision-making and to provide the rationalization behind these decisions driving resource allocation and spending for health technology products. Furthermore, HTA agencies make the decision-making process more transparent. The HTA approach involves evaluating multiple aspects of a new product’s value in order to maximize health gain provided within the setting of limited resources.

Objective The aim of this study was to investigate the impact of methodological choices in a meta-analysis of real-world evidence (RWE) comparing three non-vitamin K antagonist oral anticoagulants with vitamin K antagonists (VKAs) for the treatment of patients with non-valvular atrial fibrillation (NVAF). Methods The meta-analysis was based on a systematic review of RWE studies enrolling incident and prevalent patients aged >/=18 years with NVAF and receiving either rivaroxaban, dabigatran, apixaban, or a VKA. Five different scenarios were considered to explore the impact of the initial meta-analysis assumptions: (1) using studies that involved only incident patients; (2) excluding studies that only reported crude values and did not consider any adjustment; (3) including all studies independently of possible database overlap; (4) using studies with data on different dosages for rivaroxaban and dabigatran; and (5) assigning quality weights to studies to assess quality of reporting. These scenarios were run on three outcomes: ischemic stroke (IS), myocardial infarction (MI), and intracranial hemorrhage (ICH). Results Across all scenarios, rivaroxaban was associated with significantly lower risks of IS and ICH than VKAs. In most scenarios, dabigatran was associated with significantly lower risks of IS and ICH. In all scenarios, apixaban was associated with a significantly lower risk of ICH. Conclusions Sensitivity analyses showed the impact of similar assumptions was different depending on the outcome, and the drug considered. The development of recommendations and guidelines for the inclusion of RWE in meta-analyses could prove useful in evaluating the effectiveness of health care interventions.

OBJECTIVES: Understanding inhaler preferences may contribute to improving adherence in COPD patients and improving long-term outcomes. This study aims to identify and quantify preferences for convenience-related inhaler attributes in French moderate-to-severe COPD patients, with discrete choice experiment (DCE) methodology. METHODS: Attributes were defined from a literature search, clinician and patient interviews: shape, dose insertion, dose preparation, dose release, dose confirmation, dose counter and reusability. An online DCE was conducted in respondents with self-reported COPD stage 2-4 recruited through a panel. The study questionnaire included twelve choice scenarios per respondent and questions on patient characteristics, treatment and disease severity. Statistical analyses used a mixed logit regression model with random effects. Utility scores were estimated for four types of inhalers: Inhaler A – soft mist inhaler; Inhaler B – reusable soft mist inhaler; Inhaler C – multi-dose dry powder inhaler; and Inhaler D – single dose dry powder inhaler. RESULTS: The study was completed by 153 patients (50 females); respondents were 50.4 years old on average; 13 different inhaler devices were reported. The most preferred inhaler is L-shaped, has dose preparation with capsule insertion and a dose counter, and is reusable. Inhaler profiles A and B had the highest utilities (mean of 1.2533 and 0.9578 respectively) compared to inhaler C (0.6315) and D (0.2200). CONCLUSIONS: This study showed statistically significant results that the strongest drivers of preference in French users of inhalation devices for COPD are shape, dose counter and reusability. Convenience-related characteristics are important to patients and should be taken into account by clinicians prescribing these devices.

Rare diseases represent a group of conditions affecting a very limited number of patients. Low profitability resulting from the small size of target population coupled with difficulties in conducting the research causes the lack of interest from the pharmaceutical industry. In order to promote research and development of medicines for rare diseases, a special ‘orphan’ legislation was introduced in a number of regions. These measures led to a significant increase in the number of approved orphan molecules. The high per patient cost of orphan drugs, as well the rapid growth of orphan drug sector, raised concerns regarding the sustainable funding of therapies for rare diseases. Rare cancers represent the majority of the current orphan drug market and are often associated with very high revenues. This chapter provides a review of orphan legislations and health technology assessment framework, analyses the position of oncology drugs on the orphan drug market and discusses future perspectives.