What, Where, and How to Collect Real-World Data and Generate Real-World Evidence to Support Drug Reimbursement Decision-Making in Asia: A reflection Into the Past and A Way Forward.

BACKGROUND: Globally, there is increasing interest in the use of real-world data (RWD) and real-world evidence (RWE) to inform health technology assessment (HTA) and reimbursement decision-making. Using current practices and case studies shared by eleven health systems in Asia, a non-binding guidance that seeks to align practices for generating and using RWD/RWE for decision-making in Asia was developed by the REAL World Data In ASia for HEalth Technology Assessment in Reimbursement (REALISE) Working Group, addressing a current gap and needs among HTA users and generators. METHODS: The guidance document was developed over two face-to-face workshops, in addition to an online survey, a face-to-face interview and pragmatic search of literature. The specific focus was on what, where and how to collect RWD/ RWE. RESULTS: All 11 REALISE member jurisdictions participated in the online survey and the first in-person workshop, 10 participated in the second in-person workshop, and 8 participated in the in-depth face-to-face interviews. The guidance document was iteratively reviewed by all working group members and the International Advisory Panel. There was substantial variation in: (a) sources and types of RWD being used in HTA, and (b) the relative importance and prioritization of RWE being used for policy-making. A list of national-level databases and other sources of RWD available in each country was compiled. A list of useful guidance on data collection, quality assurance and study design were also compiled. CONCLUSION: The REALISE guidance document serves to align the collection of better quality RWD and generation of reliable RWE to ultimately inform HTA in Asia.

"What's Keeping Me Up at Night?" Reflections on the COVID-19 Pandemic in Asia.

OBJECTIVES: The 2021 Health Technology Assessment International (HTAi) Asia Policy Forum (APF) aimed to explore the challenges and opportunities presented by the global COVID-19 pandemic for health systems and industry in the Asia region, to discuss how HTA changed during the pandemic, and what its role may be moving forward into a postpandemic era. METHODS: Discussions during the virtual 2021 APF, informed by a premeeting survey of HTA agencies and industry attendees from the region describing their experience during the pandemic, form the basis of this paper. RESULTS: During the pandemic, regulatory approval for COVID-related technologies was fast-tracked with fewer evidentiary requirements, and little or no HTA being conducted before these technologies were implemented in health systems in the region. "Living HTA" incorporating real-world evidence (RWE) as it was generated became part of the HTA landscape. In comparison, non-COVID technologies experienced regulatory approval and HTA delays. A major concern of APF members was future pandemic preparedness, and to ensure that lessons are learned from COVID-19. Governments need to continue to invest in innovation and allow early regulatory approvals with the increased use of RWE. Capacity building was identified as a key investment, including capacity in HTA, modeling, as well as local production of necessary supplies and equipment. Finally, collaboration at all levels of the health system was viewed as vital. CONCLUSIONS: Post-COVID, different forms of HTA must be embraced as part of the new HTA landscape in addition to increased intra- and intercountry collaboration across all sectors of the health system, including regulatory bodies.

Changes in five-year survival for people with acute leukaemia in South Australia, 1980-2016.

OBJECTIVES: To examine population changes in 5-year survival for people in South Australia diagnosed with acute leukaemia during 1980-2016, by socio-demographic characteristics. DESIGN, SETTING: Retrospective analysis of South Australian Cancer Registry data for the period 1980-2016. PARTICIPANTS: All South Australian residents diagnosed with primary acute lymphoblastic leukaemia (ALL) or acute myeloid leukaemia (AML) during 1980-2016. MAIN OUTCOME MEASURES: 5-year disease-specific survival and disease-specific mortality. RESULTS: Crude 5-year disease-specific survival was 58% (95% CI, 54-61%) for the 1035 people diagnosed with ALL during 1980-2016, and 18% (95% CI, 17-20%) for the 2814 people diagnosed with AML. Survival improved steadily across the study period: from 44% (95% CI, 35-52%) for people with ALL diagnosed during 1980-1984 to 69% (95% CI, 63-75%) for those diagnosed during 2010-2016; and from 9% (95% CI, 5-15%) to 23% (95% CI, 20-26%) for people diagnosed with AML. Disease-specific mortality increased with age, but was not influenced by socio-economic status or remoteness of residence. After adjusting for other factors, rates of change in risk of leukaemia-related death were greater for younger than older patients with ALL (for interaction: P = 0.004) or AML (P = 0.005), but were not significantly influenced by socio-economic status or remoteness. CONCLUSION: Five-year survival for people with acute leukaemia in South Australia continuously improved during 1980-2016, and socio-economic status and remoteness did not influence survival. It improved markedly for younger patients (under 50 years of age). However, survival is still relatively poor, especially for people over 50 years with AML.

Real-world data for health technology assessment for reimbursement decisions in Asia: current landscape and a way forward.

There is growing interest globally in using real-world data (RWD) and real-world evidence (RWE) for health technology assessment (HTA). Optimal collection, analysis, and use of RWD/RWE to inform HTA requires a conceptual framework to standardize processes and ensure consistency. However, such framework is currently lacking in Asia, a region that is likely to benefit from RWD/RWE for at least two reasons. First, there is often limited Asian representation in clinical trials unless specifically conducted in Asian populations, and RWD may help to fill the evidence gap. Second, in a few Asian health systems, reimbursement decisions are not made at market entry; thus, allowing RWD/RWE to be collected to give more certainty about the effectiveness of technologies in the local setting and inform their appropriate use. Furthermore, an alignment of RWD/RWE policies across Asia would equip decision makers with context-relevant evidence, and improve timely patient access to new technologies. Using data collected from eleven health systems in Asia, this paper provides a review of the current landscape of RWD/RWE in Asia to inform HTA and explores a way forward to align policies within the region. This paper concludes with a proposal to establish an international collaboration among academics and HTA agencies in the region: the REAL World Data In ASia for HEalth Technology Assessment in Reimbursement (REALISE) working group, which seeks to develop a non-binding guidance document on the use of RWD/RWE to inform HTA for decision making in Asia.

Sustainability of healthcare systems in Asia: exploring the roles of horizon scanning and reassessment in the health technology assessment landscape.

OBJECTIVES: The 2019 Health Technology Assessment International (HTAi) Asia Policy Forum (HAPF) discussed the role of horizon scanning (HS) and health technology reassessment (HTR) in supporting sustainable healthcare in Asia. METHODS: Discussions and presentations at the 2019 HAPF, informed by a literature review, results of a premeeting survey, and case studies of HTA agencies from the region form the basis of this paper. RESULTS: Five of the fourteen HTA agencies surveyed have established or are developing HS systems (HSSs), and six reported some experience with HTR. Although there were many differences in the respective HSSs, all were proactive and identified technologies within a 1-3-year time horizon. Commonalities included the criteria used to prioritize the technologies including burden and rarity of the disease, and cost to the health system and patients. Experience in HTR was not as extensive with most HTR activity being conducted on an ad hoc basis. Challenges for both HS and HTR include a lack of HTA capacity and good quality data, as well as a need for transparency and collaboration with industry. CONCLUSIONS: With developing universal health care and HTA capacity in many countries in Asia, HS and HTR are in their infancy. Whilst several countries in the region are experienced in all facets of HTA, other countries are developing their HTA skill base. As such, there was a clear appetite for setting up a collaborative network in the Asia region to facilitate information sharing around HTA activities, and more specifically, HS and HTR methodologies, experiences, and assessments.

Improving Access to High-Cost Technologies in the Asia Region.

OBJECTIVES: Discussions at the Health Technology Assessment International (HTAi) Asia Policy Forum (HAPF) aimed to understand the meaning of "high-cost technologies," and to explore mechanisms to increase access to these technologies in publicly funded health systems in the Asia region. METHODS: Discussions and presentations at the 2018 HAPF, informed by a literature review and a premeeting survey of HTA agencies and industry, form the basis of this paper. RESULTS: Challenges payers in the public health system face when investing in high-cost technologies include a lack of data, especially real-world data, affordability, and the budgetary impact of high-cost technologies. Managed entry schemes (MES) are one means to enable earlier access to high-cost technologies, or at reduced cost to the system. Most countries surveyed had used an MES to introduce a new health technology and most industry representatives had experience with financial-based MES, such as discounts or rebates, with most put in place to increase access to pharmaceuticals. Little experience of outcome-based or evidence-generation MES was reported. CONCLUSIONS: Although it is early days in the implementation of MES in Asia, they have the potential to play an important role enabling access to new, mainly pharmaceutical, health technologies. The development of a "road map" of MES in the region should outline the intent and need for a MES, articulating the "rules of engagement" for all stakeholders-patients, providers, payers, and industry-which will assist countries to clearly identify the problem trying to be solved, and how an MES can be part of the solution.

OVERCOMING THE BARRIERS TO ACHIEVING UNIVERSAL HEALTH CARE IN THE ASIAN REGION.

OBJECTIVES: The Health Technology Assessment International (HTAi) Asia Policy Forum (HAPF) met to discuss the challenges of achieving universal health care (UHC) in Asia. METHODS: Group discussions and presentations at the 2017 HAPF, informed by a background paper, including a literature review and the results of pre-meeting surveys of health technology assessment (HTA) agencies and industry, formed the basis of this article. RESULTS: Affordability was identified as the greatest barrier to establishing UHC; however, other impediments include the lack of political will to implement UHC, and the cultural issue of deference to expert opinion instead of evidence-based assessments. Although HTA was identified as an important prioritization tool when adding new technologies to benefit packages, it is used inconsistently in the region, resulting in a less transparent decision-making process for stakeholders. Although regional challenges exist around real-world data (RWD), including a lack of capacity to enable information and data sharing, most policy or funding decision makers in the region have access to data. However, there appears to be a disconnect with the experience of industry, whose representatives identify the lack of RWD as their primary issue. To overcome these issues, both HTA agencies and industry agree that collaboration and transparency should be fostered to support the development of robust evidence generation in the region. CONCLUSIONS: There is a willingness for HTA agencies and industry to collaborate to develop HTA methodology for the prioritization of technologies in the Asia region that support healthcare systems to achieve the ultimate outcome of UHC.

Predicting Perioperative Transfusion in Elective Hip and Knee Arthroplasty: A Validated Predictive Model.

BACKGROUND: Preoperative anemia is a significant predictor of perioperative erythrocyte transfusion in elective arthroplasty patients. However, interactions with other patient and procedure characteristics predicting transfusion requirements have not been well studied. METHODS: Patients undergoing elective primary total hip arthroplasty or total knee arthroplasty at a tertiary hospital in Adelaide, South Australia, Australia, from January 2010 to June 2014 were used to identify preoperative predictors of perioperative transfusion. A logistic regression model was developed and externally validated with an independent data set from three other hospitals in Adelaide. RESULTS: Altogether, 737 adult patients in the derivation group and 653 patients in the validation group were included. Binary logistic regression modeling identified preoperative hemoglobin (odds ratio, 0.51; 95% CI, 0.43 to 0.59; P < 0.001 for each 1 g/dl increase), total hip arthroplasty (odds ratio, 3.56; 95% CI, 2.39 to 5.30; P < 0.001), and females 65 yr of age and older (odds ratio, 3.37; 95% CI, 1.88 to 6.04; P = 0.01) as predictors of transfusion in the derivation cohort. CONCLUSIONS: Using a combination of patient-specific preoperative variables, this validated model can predict transfusion in patients undergoing elective hip and knee arthroplasty. The model may also help to identify patients whose need for transfusion may be decreased through preoperative hemoglobin optimization.

Outcomes of lymphoma in South Australia, 1977-2007.

OBJECTIVE: To determine survival rates of patients with lymphoma in South Australia. DESIGN AND SETTING: De-identified data from the SA Cancer Registry on all patients with lymphoma were analysed, as well as the subgroup treated at the Royal Adelaide Hospital (RAH). For non-Hodgkin lymphoma (NHL), we used the International Working Formulation (IWF) grading. SA and RAH data on survival rates were compared with those for the whole of Australia and the United States. PATIENTS: All patients diagnosed with lymphoma and treated in SA in 1977-2007. OUTCOME MEASURES: 5-year survival rates for patients with lymphoma, by type of lymphoma and age. RESULTS: Of the total of 8651 patients with lymphoma, 939 were classified as having Hodgkin lymphoma (HL) and 7712 as having NHL. Of those with NHL, 1805 had low-grade, 3576 intermediate-grade, and 510 high-grade NHL. In another 1821 patients, the data were insufficient to make an IWF grading. There was a substantial increase in 5-year survival rates for patients with lymphoma between 1977 and 2007 in SA. While the increase in 5-year survival rates for HL was 7.6 percentage points, survival rates peaked at 88%. For NHL, there was an 18.7 percentage points increase in 5-year survival rates. The first significant increase of 7 percentage points was associated with the introduction of bone marrow transplantation; this was maintained with the increase in 5-year survival rates reaching 14 percentage points by 1995-1999. Since 1999, there has been a further increase of 5 percentage points in 5-year survival rates with the introduction of rituximab. CONCLUSION: Outcomes in patients with NHL have improved significantly, most likely because of the use of bone marrow transplantation and rituximab. Hospital- and state-based cancer registry data reflect the reality of population outcomes and the impact of new technologies.

Value of magnetic resonance cholangiopancreatography in the diagnosis of biliary abnormalities in postcholecystectomy patients: a probabilistic cost-effectiveness analysis of diagnostic strategies.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is considered the gold standard for imaging of the biliary tract but is associated with complications. Less invasive imaging techniques, such as magnetic resonance cholangiopancreatography (MRCP), have a much lower complication rate. The accuracy of MRCP is comparable to that of ERCP, and MRCP may be more effective and cost-effective, particularly in cases for which the suspected prevalence of disease is low and further intervention can be avoided. A model was constructed to compare the effectiveness and cost-effectiveness of MRCP and ERCP in patients with a previous history of cholecystectomy, presenting with abdominal pain and/or abnormal liver function tests. METHODS: Diagnostic accuracy estimates came from a systematic review of MRCP. A decision analytic model was constructed to represent the diagnostic and treatment pathway of this patient group. The model compared the following two diagnostic strategies: (i) MRCP followed with ERCP if positive, and then management based on ERCP; and (ii) ERCP only. Deterministic and probabilistic analyses were used to assess the likelihood of MRCP being cost-effective. Sensitivity analyses examined the impact of prior probabilities of common bile duct stones (CBDS) and test performance characteristics. The outcomes considered were costs, quality-adjusted life years (QALYs), and cost per additional QALY. RESULTS: The deterministic analysis indicated that MRCP was dominant over ERCP. At prior probabilities of CBDS, less than 60 percent MRCP was the less costly initial diagnostic test; above this threshold, ERCP was less costly. Similarly, at probabilities of CBDS less than 68 percent, MRCP was also the more effective strategy (generated more QALYs). Above this threshold, ERCP became the more effective strategy. Probabilistic sensitivity analyses indicated that, in this patient group for which there is a low to moderate probability of CBDS, there was a 59 percent likelihood that MRCP was cost-saving, an 83 percent chance that MRCP was more effective with a higher quality adjusted survival, and an 83 percent chance that MRCP had a cost-effectiveness ratio more favorable than dollars 50,000 per QALY gained. CONCLUSIONS: Costs and cost-effectiveness are dependent upon the prior probability of CBDS. However, probabilistic analysis indicated that, with a high degree of certainty, MRCP was the more effective and cost-effective initial test in postcholecystectomy patients with a low to moderate probability of CBDS.

Protecting our vulnerable food supply.

From farmyard to dinner table, our food supply presents ample opportunity for dangerous microorganisms or their products to thrive and infect or intoxicate human beings, often with harmful and sometimes fatal results. Traditional controls to protect the food supply include, but are not limited to, law and regulation. But law and regulation are only enablers, an underpinning. Most important to protection of the food supply is organizational leadership and commitment at federal, state, and local levels of government to protect the public's health. This article provides examples of such leadership in locales as diverse as Australia, New Zealand, and Genesee County, Michigan. Even when a supportive law is in place and the will and resources to make the law work exist, competing political and economic world-views are constantly at work to amend the law and thus adversely affect the public's health.