Health technology assessment criteria as drivers of coverage with managed entry agreements: a case study of cancer medicines in four countries.

BACKGROUND: Managed entry agreements (MEAs) continue to emerge in health technology assessment (HTA)-based decision-making, to address evidentiary uncertainties arising therein. Evidence on the HTA criteria that influence MEAs' uptake remains scarce. This study explores the HTA criteria that determine (i) if an HTA funding decision will be listed with conditions (LWC) other than a MEA, or with a MEA as a condition (LWCMEA), and ii) the MEA type implemented (i.e., financial, outcomes based, or combination). METHODS: HTA reports of all oncology medicines approved since 2009 in Australia, England, Scotland, and Sweden were searched to capture the clinical/economic evidence uncertainties raised in the decision-making process, the Social Value Judgements (SVJs) considered therein and the final coverage decision. Binary and multinomial logit models captured the probability (odds ratio (OR)) of a coverage decision being LWCMEA vs. LWC, and of the MEA being financial, outcomes based, or combination, based on the HTA criteria studied. RESULTS: 23 (12%) LWC and 163 (88%) LWCMEA decisions were identified; 136 (83.4%) comprised financial, 10 (6.2%) outcomes based and 17 (10.4%) combination MEAs. LWCMEA decisions were driven by economic model utilities' uncertainties (7.16 < OR < 26.7, p < .05), and the innovation (8.5 < OR < 11.7, p < .05) SVJ. Outcomes based contracts were influenced by clinical evidence (OR = 69.2, p < .05) and relevance to clinical practice (OR = 26.4, p < .05) uncertainties, and rarity (OR = 46.2, p < .05) and severity (OR = 23.3, p < .05) SVJs. Financial MEAs were influenced by innovation (8.9 < OR < 9.3, p < .05) and societal impact (OR = 17.7, p < .0001) SVJs. CONCLUSIONS: This study provides an empirical framework on the HTA criteria that shape payers' preferences in funding with MEAs, when faced with uncertainty.

Impact of Managed Entry Agreements on availability of and timely access to medicines: an ex-post evaluation of agreements implemented for oncology therapies in four countries.

BACKGROUND: Despite the increased utilisation of Managed Entry Agreements (MEAs), empirical studies assessing their impact on achieving better access to medicines remains scarce. In this study we evaluated the role of MEAs on enhancing availability of and timely access to a sample of oncology medicines that had received at least one prior rejection from reimbursement. METHODS: Funding decisions and their respective timelines for all oncology medicines approved between 2009 and 2018 in Australia, England, Scotland and Sweden were studied. A number of binary logit models captured the probability (Odds ratio (OR)) of a previous coverage rejection being reversed to positive after resubmission with vs. without a MEA. Gamma generalised linear models were used to understand if there is any association between time to final funding decision and the presence of MEA, among other decision-making variables, and if so, the strength and direction of this association (Beta coefficient (B)). RESULTS: Of the 59 previously rejected medicine-indication pairs studied, 88.2% (n = 45) received a favourable decision after resubmission with MEA vs. 11.8% (n = 6) without. Average time from original submission to final funding decision was 404 (± 254) and 452 (± 364) days for submissions without vs. with MEA respectively. Resubmissions with a MEA had a higher likelihood of receiving a favourable funding decision compared to those without MEA (43.36 < OR < 202, p < 0.05), although approval specifically with an outcomes-based agreement was associated with an increase in the time to final funding decision (B = 0.89, p < 0.01). A statistically significant decrease in time to final funding decision was observed for resubmissions in Australia and Scotland compared to England and Sweden, and for resubmissions with a clinically relevant instead of a surrogate endpoint. CONCLUSIONS: MEAs can improve availability of medicines by increasing the likelihood of reimbursement for medicines that would have otherwise remained rejected from reimbursement due to their evidentiary uncertainties. Nevertheless, approval with a MEA can increase the time to final funding decision, while the true, added value for patients and healthcare systems of the interventions approved with MEAs in comparison to other available interventions remains unknown.

Determinants of Managed Entry Agreements in the context of Health Technology Assessment: a comparative analysis of oncology therapies in four countries.

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.

Does external reference pricing deliver what it promises? Evidence on its impact at national level.

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, cost-containment, 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.

Health related quality of life aspects not captured by EQ-5D-5L: Results from an international survey of patients.

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.

DIFFERENTIATION OF HEALTH-RELATED QUALITY OF LIFE OUTCOMES BETWEEN FIVE DISEASE AREAS: RESULTS FROM AN INTERNATIONAL SURVEY OF PATIENTS.

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.

Using IMPrESS to guide policy change in multiple sclerosis.

The International MultiPlE Sclerosis Study (IMPrESS) studied the significant impact of multiple sclerosis (MS) on the health and well-being of both people with the disease and their caregivers, along with its broader socioeconomic 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 socioeconomic 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 socioeconomic results for individuals.