Sebastian Salas-Vega

Assessment of overall survival, quality of life, and safety benefits associated with new cancer medicines

Importance There is a dearth of evidence examining the impact of newly licensed cancer medicines on therapy. This information could otherwise support clinical practice, and promote value-based decision-making in the cancer drug market. Objective To evaluate the comparative therapeutic value of all new cancer medicines approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) between 2003 and 2013. Design, Setting, and Participants We used a narrative synthesis approach to systematically synthesize and analyze English, French, and Australian health technology assessments (HTAs) of all new cancer medicines licensed in the United States and Europe between 2003 and 2013. Interventions Sixty-two new molecular entities with a primary oncology indication. Main Outcomes and Measures Overall survival (OS), quality of life (QoL), and safety. Results Of the 62 new active cancer molecules approved by the FDA and EMA between 2003 and 2013, 53 were appraised by English, French, or Australian HTA agencies through May 2015. Of these 53 drugs, 23 (43%) increased OS by 3 months or longer, 6 (11%) by less than 3 months, and 8 (15%) by an unknown magnitude; there was no evidence to suggest that the remaining 16 (30%) increased OS over best alternative treatments. Where overall survival gains could be quantified, all new cancer drugs were associated with a mean (SE) total increase in OS of 3.43 (0.63) months over the treatments that were available in 2003. Drug-related improvements in OS were, however, widely distributed across therapeutic targets—ranging between 0 (thyroid, ascites) and 8.48 months (breast cancers)—and were sometimes based on modeled data, indirect or nonactive comparisons, or nonvalidated evidence. Although 22 (42%) of 53 new medicines were associated with an increase in QoL, 24 (45%) were also associated with reduced patient safety. Of the 53 new cancer drugs, 42 (79%) were associated with at least some improvement in OS, QoL, or safety. Conclusions and Relevance Although innovation in the oncology drug market has contributed to improvements in therapy, the magnitude and dimension of clinical benefits vary widely, and there may be reasons to doubt that claims of efficacy reflect real-world effectiveness exactly. These findings raise important questions for clinical decision-making and value-based policy.

Availability, cost, and prescription patterns of antihypertensive medications in primary health care in China: a nationwide cross-sectional survey

BACKGROUND Around 200 million adults in China have hypertension, but few are treated or achieve adequate control of their blood pressure. Available and affordable medications are important for successfully controlling hypertension, but little is known about current patterns of access to, and use of, antihypertensive medications in Chinese primary health care. METHODS We used data from a nationwide cross-sectional survey (the China Patient-Centered Evaluative Assessment of Cardiac Events Million Persons Project primary health care survey), which was undertaken between November, 2016 and May, 2017, to assess the availability, cost, and prescription patterns of 62 antihypertensive medications at primary health-care sites across 31 Chinese provinces. We surveyed 203 community health centres, 401 community health stations, 284 township health centres, and 2474 village clinics to assess variation in availability, cost, and prescription by economic region and type of site. We also assessed the use of high-value medications, defined as guideline-recommended and low-cost. We also examined the association of medication cost with availability and prescription patterns. FINDINGS Our study sample included 3362 primary health-care sites and around 1 million people (613 638 people at 2758 rural sites and 478 393 people at 604 urban sites). Of the 3362 sites, 8·1% (95% CI 7·2-9·1) stocked no antihypertensive medications and 33·8% (32·2-35·4) stocked all four classes that were routinely used. Village clinics and sites in the western region of China had the lowest availability. Only 32·7% (32·2-33·3) of all sites stocked high-value medications, and few high-value medications were prescribed (11·2% [10·9-11·6] of all prescription records). High-cost medications were more likely to be prescribed than low-cost alternatives. INTERPRETATION China has marked deficiencies in the availability, cost, and prescription of antihypertensive medications. High-value medications are not preferentially used. Future efforts to reduce the burden of hypertension, particularly through the work of primary health-care providers, will need to improve access to, and use of, antihypertensive medications, paying particular attention to those with high value. FUNDING CAMS Innovation Fund for Medical Science, the Entrusted Project from the China National Development and Reform Commission, and the Major Public Health Service Project from the Ministry of Finance of China and National Health and Family Planning Commission of China.

A study of whether automated Diabetic Retinopathy Image Assessment could replace manual grading steps in the English National Screening Programme

Objectives Diabetic retinopathy screening in England involves labour intensive manual grading of digital retinal images. We present the plan for an observational retrospective study of whether automated systems could replace one or more steps of human grading. Methods Patients aged 12 or older who attended the Diabetes Eye Screening programme, Homerton University Hospital (London) between 1 June 2012 and 4 November 2013 had macular and disc-centred retinal images taken. All screening episodes were manually graded and will additionally be graded by three automated systems. Each system will process all screening episodes, and screening performance (sensitivity, false positive rate, likelihood ratios) and diagnostic accuracy (95% confidence intervals of screening performance measures) will be quantified. A sub-set of gradings will be validated by an approved Reading Centre. Additional analyses will explore the effect of altering thresholds for disease detection within each automated system on screening performance. Results 2,782/20,258 diabetes patients were referred to ophthalmologists for further examination. Prevalence of maculopathy (M1), pre-proliferative retinopathy (R2), and proliferative retinopathy (R3) were 7.9%, 3.1% and 1.2%, respectively; 4749 (23%) patients were diagnosed with background retinopathy (R1); 1.5% were considered ungradable by human graders. Conclusions Retinopathy prevalence was similar to other English diabetic screening programmes, so findings should be generalizable. The study population size will allow the detection of differences in screening performance between the human and automated grading systems as small as 2%. The project will compare performance and economic costs of manual versus automated systems.

A comparative study of drug listing recommendations and the decision-making process in Australia, the Netherlands, Sweden, and the UK

Drug listing recommendations from health technology assessment (HTA) agencies often fail to coincide with one another. We conducted a comparative analysis of listing recommendations in Australia (PBAC), the Netherlands (CVZ), Sweden (TLV) and the UK (NICE) over time, examined interagency agreement, and explored how process-related factors-including time delay between HTA evaluations, therapeutic indication and orphan drug status, measure of health economic value, and comparator-impacted decision-making in drug coverage. Agreement was poor to moderate across HTA agency listing recommendations, yet it increased as the delay between HTA agency appraisals decreased, when orphan drugs were assessed, and when medicines deemed to provide low value (immunosuppressants, antineoplastics) were removed from the sample. International differences in drug listing recommendations seem to occur in part due to inconsistencies in how the supporting evidence informs assessment, but also to differences in how domestic priorities shape the value-based decision-making process.

Big Data and Health Care: Challenges and Opportunities for Coordinated Policy Development in the EU

Abstract—As global policy makers prioritize big data policy, it is important to try to outline expected outcomes vis-à-vis health sector objectives. We identify initiatives aimed at promoting the use of big data in European Union (EU) health care, highlight expected challenges, and use these to evaluate EU big data policy developments to the extent that they are able to advance health sector priorities. A comprehensive approach is used to capture and examine peer-reviewed and gray literature publications on the use of big data in global health systems. This approach involved electronic database and specialist website searching, as well as complementary use of search engines and qualitative inputs from key EU policy stakeholders. Ongoing health data initiatives revolve around data center development, confidentiality and security, e-health and m-health, and genomics and bioinformatics. The literature acknowledges several main challenges to the successful integration of big data in health care, classified as either ethical (confidentiality and data security, access to information) or technical (data reliability, interoperability, data management and governance). EU data policy has started to address these issues, though additional work remains. A larger outstanding challenge is the lack of a comprehensive health and research policy strategy for big data that targets sectoral objectives. It remains unclear how big data integration will affect the quality and performance of health care in the EU. The promises of big data are being eroded by a failure to develop a coherent approach to adequately address conceptual, ethical, and technical challenges pertaining to its use within EU health systems.