BACKGROUND:In this paper we discuss and present evidence on whether a generic Health Related Quality of Life (HRQoL) measurement tool, the EQ-5D-5L, captures the dimensions of quality of life (QoL) which patients consider significant. METHODS: An online survey, of individuals with a chronic condition, mainly breast cancer (BC), blood cancers (BLC), rheumatoid arthritis (RA), asthma, and rare diseases (RD) was conducted to collect data on HRQoL and important QoL aspects that respondents thought were not captured by the EQ-5D-5L. Patient organisations across 47 countries were invited to voluntarily share the survey tool with their membership network. RESULTS: 767 responses from 38 countries showed that important QoL aspects were not captured by EQ-5D-5L for 51% of respondents, including fatigue (19%) and medication side effects (12%), among others. Fatigue (17%) was also the most commonly reported QoL aspect that changed over the course of patients'illness, suggesting that the current version of the EQ-5D-5L might miss capturing significant clinical changes in important QoL domains. CONCLUSIONS: Utilisation of the EQ-5D-5L in HRQoL measurement raises inconsistencies in capturing QoL attributes and changes in disease-specific patient populations. Further research is needed to clarify the extent to which other generic HRQoL measurement tools capture the aspects of health that really matter for patients. Utility Analysis.Highlights 1. EQ-5D-5L didn't capture key QoL dimensions for more than half of the sample.2. Several QoL aspects, notably fatigue, were identified as overlooked by EQ-5D-5L.3. Around 60% of patients reported changes on key QoL aspects during their illness.4. It is unknown if other generic HRQoL measurement tools face the same challenges.

Background External reference pricing (ERP) is widely used to regulate pharmaceutical prices and help determine reimbursement. Its implementation varies substantially across countries, making it difficult to study and understand its impact on key policy objectives. Objectives To assess the evidence on ERP in different settings and its impact on key health policy objectives, notably, costcontainment, pharmaceutical price levels, drug use, equity, efficiency, availability, affordability and industrial policy; and second, to critically assess the quality of evidence on ERP. Methods Primary and secondary data collection through a survey of leading experts and a systematic literature review, respectively, over the 2000-2017 period. Results Forty five studies were included in the systematic review (January 2000-December 2016). Primary evidence was gathered via survey distribution to experts in 21 countries (January-July 2017). ERP contributes to cost-containment, but this is a short-term effect highly dependent on the way ERP is designed and implemented. Low prices, as a result of ERP, can undermine the availability of medicines and lead to launch delays or product withdrawals. Downward price convergence can hamper investment in innovation. ERP does not seem to promote efficiency in achieving health system goals. As evidence is weak, results need to be interpreted with caution. Conclusions ERP has not regulated prices efficiently and has unintended consequences that reduce the benefits arising from it. If ERP is carefully designed with minimal price revisions, prudent selection of basket size and countries, and consideration of transaction prices, it could be a more effective mechanism enhancing welfare, equitable access to medicines within countries and help promote industry innovation.

Background Managed Entry Agreements (MEAs) are increasingly used to address uncertainties arising in the Health Technology Assessment (HTA) process due to immature evidence of new, high-cost medicines on their real-world performance and cost-effectiveness. The literature remains inconclusive on the HTA decision-making factors that influence the utilization of MEAs. We aimed to assess if the uptake of MEAs differs between countries and if so, to understand which HTA decision-making criteria play a role in determining such differences. Methods All oncology medicines approved since 2009 in Australia, England, Scotland, and Sweden were studied. Four categories of variables were collected from publicly available HTA reports of the above drugs: (i) Social Value Judgments (SVJs), (ii) Clinical/Economic evidence submitted, (iii) Interpretation of this evidence, and (iv) Funding decision. Conditional/restricted decisions were coded as Listed With Conditions (LWC) other than an MEA or LWC including an MEA (LWCMEA). Cohen's κ-scores measured the inter-rater agreement of countries on their LWCMEA outcomes and Pearson's chi-squared tests explored the association between HTA variables and LWCMEA outcomes. Results A total of 74 drug-indication pairs were found resulting in n = 296 observations; 8 percent (n = 23) were LWC and 55 percent (n = 163) were LWCMEA. A poor-to-moderate agreement existed between countries (−.29 < κ < .33) on LWCMEA decisions. Cross-country differences within the LWCMEA sample were partly driven by economic uncertainties and largely driven by SVJs considered across agencies. Conclusions A set of HTA-related variables driving the uptake of MEAs across countries was identified. These findings can be useful in future research aimed at informing country-specific, “best-practice” guidelines for successful MEA implementation.

Short summaryThe IMPrESS (International-MultiPlE-Sclerosis-Study) studied the significant impact of multiple sclerosis (MS) on the health and wellbeing of both people with the disease, and their caregivers, along with its broader socio-economic impact. Results confirmed that there is an urgent need to achieve better outcomes for people with MS. This paper uses results from the IMPRESS to present new international evidence on the socio-economic burden of MS and discuss the merits of a likely paradigm shift in the management of MS towards the use of better (and more accurate) diagnostic follow-up to monitor disease progression and the earlier use of disease-modifying-treatments (DMTs) to achieve better clinical, quality of life and socio-economic results for individuals. IntroductionMultiple-sclerosis (MS) is the most common cause of disability among central-nervous-system (CNS) diseases. MS is associated with a high cost of illness, both in terms of direct and indirect costs. Given that the onset of MS is in early adult life (average onset at 29 years of age) lasting over an individual's lifetime, there are huge costs relating to productivity losses. There is also a significant impact on the families of people with MS (PWMS).Treating until no-evidence-of-disease-activity (NEDA) is reached, including no relapses, no increase in disability and no new or active (enhancing) lesions on their MRI scans, is gaining more popularity 1 and . The IMPrESS (International-MultiPlE-Sclerosis-Study) 4 is the first study that: present the evidence for, and generate debate on, the merits of a policy change in the management of MS, including the use of better (and more accurate) diagnostic follow up to monitor disease progression and the earlier use of DMTs to achieve better outcomes for individuals; and also assess the socio-economic and personal impact of such a policy change compared to the current status. The IMPrESS (International MultiPlE Sclerosis Study)The . Greater values in utility were accompanied by lower disability and increased satisfaction values with the healthcare service received. Fatigue and weakness, bladder or balance problems were the most frequently reported factors that had a significant impact on PWMS life and they believed a new MS treatment should keep them under control. It can be argued that other health state factors beyond EQ-5D-5L are (more) important to PWMS (appendix 5). Evidence from the literature 7 showed that MS-related complications, including severe urinary tract infections, constipation, fractures and falls (due to increased weakness and fatigue), and pressure sores are major reasons for hospital admissions with significant socioeconomic consequences. This highlights the importance of identifying the most appropriate utility measure to be adopted. Caregivers reported better quality of life compared with PWMS (73% vs. 59% of perfect health), whereas both caregivers and the person they are caring for reported a mild level of discomfort/disability. Primary data collection from PWMS, their care...

Objectives:Health-related quality of life (HRQoL) data generated by generic, preference-based instruments (i.e., EQ-5D) are highly demanded in health policy decision making, because they allow for direct comparisons of HRQoL outcomes between disease areas. We aimed to quantify HRQoL outcomes in breast cancer (BC), rheumatoid arthritis (RA), multiple sclerosis (MS), rare cancers (RC), and rare disease (RD) patients and understand the patterns that differentiate HRQoL outcomes between these disease areas, and more specifically between rare and more common disease population groups.Methods:An international, Web survey of patients measured HRQoL (EQ-5D-5L), self-perceived health (EQ-5D-5L Visual Analogue Scale), and additional QoL dimensions, such as patient disability level.Results:We received 675 completed responses. Average utility loss was 53.5 percent, 32.5 percent, and 33.3 percent for RD, RA, and MS patients, respectively, in contrast to 18.6 percent for BC and RC patients. Statistically significant differences (p < .05) were observed between disease groups in all EQ-5D-5L domain outcomes, apart from that of “Anxiety/Depression.” Severe and/or extreme problems were reported in performing usual activities for RD and RC (34 percent and 13 percent of overall problems reported respectively), mobility for MS (18 percent), pain/discomfort for RA (13 percent), and anxiety/depression for BC (7 percent) patients.Conclusions:We demonstrated significant differences in the dimensions that drive HRQoL outcomes between rare and more common diseases and showcased that the same EQ-5D utility may reflect very different severities depending on the patient population under investigation. Future research should examine whether outcomes in other, critical HRQoL domains not included in generic measures also highlight significant differences across disease areas.