Cost-effectiveness of peer-delivered physical activity promotion and maintenance programs for initially sedentary breast cancer survivors.

The evidence for the survival and health benefits of physical activity (PA) among cancer survivors is well documented. However, it has been challenging to maintain PA among cancer survivors. To evaluate the cost-effectiveness of peer support to encourage maintenance of moderate-to-vigorous physical activity (MVPA) among breast cancer survivors. Participants were randomized into Reach Plus Message (weekly text/email messages), Reach Plus Phone (monthly phone calls) or Reach Plus (a self-monitoring intervention) over 6 months after an initial adoption phase. We calculated the incremental cost-effectiveness ratios (ICER) in terms of quality-adjusted years life years (QALYs) and self-reported MVPA, from the payer's budgetary and societal perspectives over 1 year. Intervention costs were collected via time logs from the trainers and peer coaches, and participant costs from the participants via surveys. For our sensitivity analyses, we bootstrapped costs and effects to construct cost-effectiveness planes and acceptability curves. The intervention that provides weekly messages from peer coaches has an ICER of $14,446 per QALY gained and $0.95 per extra minute of MVPA per day over Reach Plus. Reach Plus Message has a 49.8% and 78.5% probability of cost-effectiveness respectively when decision makers are willing to pay approximately $25,000 per QALY and $10 per additional minute of MVPA. Reach Plus Phone, which requires tailored monthly telephone calls, costs more than Reach Plus Message but yields less QALY and self-reported MVPA at 1 year. Reach Plus Message may be a viable and cost-effective intervention strategy to maintain MVPA among breast cancer survivors.

Sustained physical activity (PA) among cancer survivors can increase survival and decrease the recurrence of cancer. However, it has been challenging to encourage cancer survivors to sustain exercise programs. In this study, we sought to understand whether two types of peer support interventions shown to sustain PA among cancer survivors can do so cost-effectively. Based on our previous study showing that weekly text messages or monthly personalized phone calls can help cancer survivors exercise more and for a longer period of time, we conducted this study to understand which intervention is more cost-effective to implement. We found that text messages are more cost-effective than personalized phone calls, costing $14,446 for every additional quality-adjusted life year gained and $0.95 for every additional minute of moderate-to-vigorous PA per week compared to the comparator group of cancer survivors who only received educational support at the beginning of the study.

Assessing the ability of an instrumental variable causal forest algorithm to personalize treatment evidence using observational data: the case of early surgery for shoulder fracture.

BACKGROUND: Comparative effectiveness research (CER) using observational databases has been suggested to obtain personalized evidence of treatment effectiveness. Inferential difficulties remain using traditional CER approaches especially related to designating patients to reference classes a priori. A novel Instrumental Variable Causal Forest Algorithm (IV-CFA) has the potential to provide personalized evidence using observational data without designating reference classes a priori, but the consistency of the evidence when varying key algorithm parameters remains unclear. We investigated the consistency of IV-CFA estimates through application to a database of Medicare beneficiaries with proximal humerus fractures (PHFs) that previously revealed heterogeneity in the effects of early surgery using instrumental variable estimators. METHODS: IV-CFA was used to estimate patient-specific early surgery effects on both beneficial and detrimental outcomes using different combinations of algorithm parameters and estimate variation was assessed for a population of 72,751 fee-for-service Medicare beneficiaries with PHFs in 2011. Classification and regression trees (CART) were applied to these estimates to create ex-post reference classes and the consistency of these classes were assessed. Two-stage least squares (2SLS) estimators were applied to representative ex-post reference classes to scrutinize the estimates relative to known 2SLS properties. RESULTS: IV-CFA uncovered substantial early surgery effect heterogeneity across PHF patients, but estimates for individual patients varied with algorithm parameters. CART applied to these estimates revealed ex-post reference classes consistent across algorithm parameters. 2SLS estimates showed that ex-post reference classes containing older, frailer patients with more comorbidities, and lower utilizers of healthcare were less likely to benefit and more likely to have detriments from higher rates of early surgery. CONCLUSIONS: IV-CFA provides an illuminating method to uncover ex-post reference classes of patients based on treatment effects using observational data with a strong instrumental variable. Interpretation of treatment effect estimates within each ex-post reference class using traditional CER methods remains conditional on the extent of measured information in the data.

Improving oncology biosimilar launches in the EU, the USA, and Japan: an updated Policy Review from the Southern Network on Adverse Reactions.

The EU, the USA, and Japan account for the majority of biological pharmacotherapy use worldwide. Biosimilar regulatory approval pathways were authorised in the EU (2006), in Japan (2009), and in the USA (2015), to facilitate approval of biological drugs that are highly similar to reference products and to encourage market competition. Between 2007 and 2020, 33 biosimilars for oncology were approved by the European Medicines Agency (EMA), 16 by the US Food and Drug Administration (FDA), and ten by the Japan Pharmaceuticals and Medical Devices Agency (PMDA). Some of these approved applications were initially rejected because of manufacturing concerns (four of 36 [11%] with the EMA, seven of 16 [44%] with the FDA, none of ten for the PMDA). Median times from initial regulatory submission before approval of oncology biosimilars were 1·5 years (EMA), 1·3 years (FDA), and 0·9 years (PMDA). Pharmacists can substitute biosimilars for reference biologics in some EU countries, but not in the USA or Japan. US regulation prohibits substitution, unless the biosimilar has been approved as interchangeable, a designation not yet achieved for any biosimilar in the USA. Japan does not permit biosimilar substitution, as prescribers must include the product name on each prescription and that specific product must be given to the patient. Policy Reviews published in 2014 and 2016 in The Lancet Oncology focused on premarket and postmarket policies for oncology biosimilars before most of these drugs received regulatory approval. In this Policy Review from the Southern Network on Adverse Reactions, we identify factors preventing the effective launch of oncology biosimilars. Introduction to the market has been more challenging with therapeutic than for supportive care oncology biosimilars. Addressing region-specific competition barriers and educational needs would improve the regulatory approval process and market launches for these biologics, therefore expanding patient access to these products in the EU, the USA, and Japan.

Associations Between Physician Supply Levels and Amenable Mortality Rates: An Analysis of Taiwan Over Nearly 4 Decades.

Access to health care is an important determinant of health, but it remains unclear whether having more physicians reduces mortality. In this study, we used Taiwan's population-level National Death Certification Registry data to investigate whether a greater supply of physicians is associated with lower rates of amenable mortality, defined as deaths that can be delayed with appropriate and timely medical treatment. Our baseline regression analysis adjusting only for age and sex shows that an increase in the number of physicians per 1000 is associated with a reduction of 1.7 (P < .01) and 0.97 (P < .01) age-standardized deaths per 100 000 for men and women, respectively. However, in our full analyses that control for socioeconomic factors and Taiwan's health insurance expansion, we find that physician supply is no longer statistically associated with amenable mortality rates. Nevertheless, we found that greater physician supply levels are associated with a reduction in deaths from ischemic heart disease (-0.13 (P < .05) for men, and -0.066 (P < .05) for women). These findings suggest that overall, physician supply is not associated with amenable mortality rates after controlling for socioeconomic factors but may help reduce amenable mortality rates in specific causes of death.

Are quality-adjusted medical prices declining for chronic disease? Evidence from diabetes care in four health systems.

Improvements in medical treatment have contributed to rising health spending. Yet there is relatively little evidence on whether the spending increase is "worth it" in the sense of producing better health outcomes of commensurate value-a critical question for understanding productivity in the health sector and, as that sector grows, for deriving an accurate quality-adjusted price index for an entire economy. We analyze individual-level panel data on medical spending and health outcomes for 123,548 patients with type 2 diabetes in four health systems: Japan, The Netherlands, Hong Kong and Taiwan. Using a "cost-of-living" method that measures value based on improved survival, we find a positive net value of diabetes care: the value of improved survival outweighs the added costs of care in each of the four health systems. This finding is robust to accounting for selective survival, end-of-life spending, and a range of values for a life-year or fraction of benefits attributable to medical care. Since the estimates do not include the value from improved quality of life, they are conservative. We, therefore, conclude that the increase in medical spending for management of diabetes is offset by an increase in quality.

Early evidence from South Carolina's Medicare-Medicaid dual-eligible financial alignment initiative: an observational study to understand who enrolled, and whether the program improved health?

BACKGROUND: Individuals dually eligible for Medicare and Medicaid coverage are among the sickest patients in the United States. Prior literature has identified a lack of care coordination or even conflicts of interest between the two programs as barriers to more efficient care and better health outcomes among dual-eligibles. The purpose of this study is to assess characteristics of dual eligibles who participated in South Carolina's 2015 voluntary Medicare-Medicaid financial alignment demonstration project, and to evaluate whether their participation led to better observable health outcomes. METHODS: We obtained all inpatient and emergency department visits, and all Medicaid outpatient visits of individuals identified as Medicare-Medicaid dual eligibles from 2011 to 2016 from South Carolina's Revenue and Fiscal Affairs Office. We employed logistic regressions to assess the characteristics of participants and quitters in the Medicare-Medicaid financial alignment demonstration project. To evaluate the impact of participation on health outcomes, we used an event study analysis that examines trends in outcomes over time, with participation in the demonstration project as the triggering event, and a difference-in-differences methodology that compares changes in health outcomes before and after participation in the demonstration project compared with a control group. RESULTS: Urban patients, female patients, and patients with heart problems, social and mental disorders, and importantly, patients with multiple comorbidities (as indicated by a higher Charlson comorbidity index) are less likely to join South Carolina's demonstration project. Once having joined, female patients and patients with a higher Charlson index appear to be more likely to quit. Those who joined did not appear to enjoy better health outcomes in the short time frame. CONCLUSIONS: Policy makers should explore and address reasons why dual eligibles with complex health problems hesitate to join the alignment project, and continue to monitor whether such a program improves health given that a prolonged period of exposure to the program may be required to achieve better health among the nation's most vulnerable patients.

Why Biologics and Biosimilars Remain So Expensive: Despite Two Wins for Biosimilars, the Supreme Court's Recent Rulings do not Solve Fundamental Barriers to Competition.

Biologics and biosimilars are medicines made from living cells that treat common and serious diseases such as cancer, diabetes, rheumatoid arthritis, and other inflammatory diseases. They are highly targeted, efficacious, and represent an increasingly important part of physicians' armamentaria in the combat against these medical conditions. Yet they are extremely expensive, costing on average $10,000-$30,000 per year and exceed $500,000 for the most expensive biologics. The advent of biosimilar drugs, or high similar copies of biologics, was supposed to help reduce costs, but thus far the cost of treatment with biologics or biosimilars has not fallen sharply in the USA. We argue that a primary hurdle is the extent of patent protection for the reference biologics that impedes greater numbers of biosimilars entering into the market. To date, of the 12 biosimilars approved for marketing by the US Food and Drug Administration (FDA), only five are commercially available. All but one of the remaining biosimilars are withheld from commercialization due to patent disputes. We argue that the market for biologics and biosimilars will become price competitive only if more biosimilars are available to patients. To this end, the process to eliminate marginally inventive patents held by the reference drug makers must be streamlined and improved. In this perspective article, we suggest actions to improve the pre-FDA approval patent resolution process known as the patent dance, the streamlined patent invalidation process known as Inter Partes Reviews, and the process of granting patents.

Avoidable Hospital Admissions From Diabetes Complications In Japan, Singapore, Hong Kong, And Communities Outside Beijing.

Improving the quality of primary care may reduce avoidable hospital admissions. Avoidable admissions for conditions such as diabetes are used as a quality metric in the Health Care Quality Indicators of the Organization for Economic Cooperation and Development (OECD). Using the OECD indicators, we compared avoidable admission rates and spending for diabetes-related complications in Japan, Singapore, Hong Kong, and rural and peri-urban Beijing, China, in the period 2008-14. We found that spending on diabetes-related avoidable hospital admissions was substantial and increased from 2006 to 2014. Annual medical expenditures for people with an avoidable admission were six to twenty times those for people without an avoidable admission. In all of our study sites, when we controlled for severity, we found that people with more outpatient visits in a given year were less likely to experience an avoidable admission in the following year, which implies that primary care management of diabetes has the potential to improve quality and achieve cost savings. Effective policies to reduce avoidable admissions merit investigation.

Generic oncology drugs: are they all safe?

Although the availability of generic oncology drugs allows access to contemporary care and reduces costs, there is international variability in the safety of this class of drugs. In this Series paper, we review clinical, policy, safety, and regulatory considerations for generic oncology drugs focusing on the USA, Canada, the European Union (EU), Japan, China, and India. Safety information about generic formulations is reviewed from one agent in each class, for heavy metal drugs (cisplatin), targeted agents (imatinib), and cytotoxic agents (docetaxel). We also review regulatory reports from Japan and the USA, countries with the largest pharmaceutical expenditures. Empirical studies did not identify safety concerns in the USA, Canada, the EU, and Japan, where regulations and enforcement are strong. Although manufacturing problems for generic pharmaceuticals exist in India, where 40% of all generic pharmaceuticals used in the USA are manufactured, increased inspections and communication by the US Food and Drug Administration are occurring, facilitating oversight and enforcement. No safety outbreaks among generic oncology drugs were reported in developed countries. For developing countries, oversight is less intensive, and concerns around drug safety still exist. Regulatory agencies should collaboratively develop procedures to monitor the production, shipment, storage, and post-marketing safety of generic oncology drugs. Regulatory agencies for each country should also aim towards identical definitions of bioequivalence, the cornerstone of regulatory approval.

Statins are Associated With a Reduced Risk of Brain Cancer: A Population-Based Case-Control Study.

The aim of this study was to investigate whether statin utilization is associated with brain cancer risk.A population-based case-control study was conducted using nationally representative claims data from the National Health Insurance Bureau in Taiwan. Cases included all patients 50 years and older who received an index diagnosis of brain cancer between 2004 and 2011. Our controls were matched by age, sex, and index date. We estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) using multiple logistic regression.We examined 213 brain cancer cases and 852 controls. The unadjusted ORs for any statin prescription was 0.77 (95% CI = 0.50-1.18) and the adjusted OR was 0.59 (95% CI = 0.37-0.96). Compared with no use of statins, the adjusted ORs were 0.68 (95% CI = 0.38-1.24) for the group having been prescribed with statins with cumulative defined daily dose (DDD) below 144.67 DDDs and 0.50 (95% CI = 0.28-0.97) for the group with the cumulative statin use of 144.67 DDDs or more.The results of this study suggest that statins may reduce the risk of brain cancer.

Travel distances, socioeconomic characteristics, and health disparities in nonurgent and frequent use of Hospital Emergency Departments in South Carolina: a population-based observational study.

BACKGROUND: Nonurgent use of hospital emergency departments (ED) is a controversial topic. It is thought to increase healthcare costs and reduce quality, but is also considered a symptom of unequal access to health care. In this article, we investigate whether convenience (as proxied by travel distances to the hospital ED and to the closest federally qualified health center) is associated with nonurgent ED use, and whether evidence of health disparities exist in the way vulnerable populations use the hospital ED for medical care in South Carolina. METHODS: Our data includes 6,592,501 ED visits in South Carolina between 2005 and 2010 from the South Carolina Budget Control Board and Office of Research and Statistics. All ED visits by South Carolina residents with unmasked variables and nonmissing urgency measures, or approximately 76% of all ED visits, are used in the analysis. We perform multivariable linear regressions to estimate correlations between (1) travel distances and observable sociodemographic characteristics and (2) measures of nonurgent ED use or frequent nonurgent ED use, as defined by the New York University ED Algorithm. RESULTS: Patients with commercial private insurance, self-pay patients, and patients with other payment sources have lower measures of nonurgent ED use the further away the ED facility is from the patients' home address. Vulnerable populations, particularly African American and Medicaid patients, have higher measures of nonurgent ED scores, and are more frequent users of the ED for both nonurgent and urgent reasons in South Carolina. At the same time, African Americans visit the hospital ED for medical conditions with higher primary care-preventable scores. CONCLUSIONS: Contrary to popular belief, convenient access (in terms of travel distances) to hospital ED is correlated with less-urgent ED use among privately insured patients and self-pay patients in South Carolina, but not publicly insured patients. Unequal access to primary care appears to exist, as suggested by African American patients' use of the hospital ED for primary care-treatable conditions while experiencing more frequent and more severe primary care-preventable conditions.

Travel distance and sociodemographic correlates of potentially avoidable emergency department visits in California, 2006-2010: an observational study.

INTRODUCTION: Use of the hospital emergency department (ED) for medical conditions not likely to require immediate treatment is a controversial topic. It has been faulted for ED overcrowding, increased expenditures, and decreased quality of care. On the other hand, such avoidable ED utilization may be a manifestation of barriers to primary care access. METHODS: A random 10% subsample of all ED visits with unmasked variables, or approximately 7.2% of all ED visits in California between 2006 and 2010 are used in the analysis. Using panel data methods, we employ linear probability and fractional probit models with hospital fixed effects to analyze the associations between avoidable ED utilization in California and observable patient characteristics. We also test whether shorter estimated road distances to the hospital ED are correlated with non-urgent ED utilization, as defined by the New York University ED Algorithm. We then investigate whether proximity of a Federally Qualified Health Center (FQHC) is correlated with reductions in non-urgent ED utilization among Medicaid patients. RESULTS: We find that relative to the reference group of adults aged 35-64, younger patients generally have higher scores for non-urgent conditions and lower scores for urgent conditions. However, elderly patients (≥65) use the ED for conditions more likely to be urgent. Relative to male and white patients, respectively, female patients and all identified racial and ethnic minorities use the ED for conditions more likely to be non-urgent. Patients with non-commercial insurance coverage also use the ED for conditions more likely to be non-urgent. Medicare and Medicaid patients who live closer to the hospital ED have higher probability scores for non-emergent visits. However, among Medicaid enrollees, those who live in zip codes with an FQHC within 0.5 mile of the zip code population centroid visit the ED for medical conditions less likely to be non-emergent. CONCLUSIONS: These patterns of ED utilization point to potential barriers to care among historically vulnerable groups, observable even when using rough estimates of travel distances and avoidable ED utilization.

Multi-Country analysis of palm oil consumption and cardiovascular disease mortality for countries at different stages of economic development: 1980-1997.

BACKGROUND: Cardiovascular diseases represent an increasing share of the global disease burden. There is concern that increased consumption of palm oil could exacerbate mortality from ischemic heart disease (IHD) and stroke, particularly in developing countries where it represents a major nutritional source of saturated fat. METHODS: The study analyzed country-level data from 1980-1997 derived from the World Health Organization's Mortality Database, U.S. Department of Agriculture international estimates, and the World Bank (234 annual observations; 23 countries). Outcomes included mortality from IHD and stroke for adults aged 50 and older. Predictors included per-capita consumption of palm oil and cigarettes and per-capita Gross Domestic Product as well as time trends and an interaction between palm oil consumption and country economic development level. Analyses examined changes in country-level outcomes over time employing linear panel regressions with country-level fixed effects, population weighting, and robust standard errors clustered by country. Sensitivity analyses included further adjustment for other major dietary sources of saturated fat. RESULTS: In developing countries, for every additional kilogram of palm oil consumed per-capita annually, IHD mortality rates increased by 68 deaths per 100,000 (95% CI [21-115]), whereas, in similar settings, stroke mortality rates increased by 19 deaths per 100,000 (95% CI [-12-49]) but were not significant. For historically high-income countries, changes in IHD and stroke mortality rates from palm oil consumption were smaller (IHD: 17 deaths per 100,000 (95% CI [5.3-29]); stroke: 5.1 deaths per 100,000 (95% CI [-1.2-11.0])). Inclusion of other major saturated fat sources including beef, pork, chicken, coconut oil, milk cheese, and butter did not substantially change the differentially higher relationship between palm oil and IHD mortality in developing countries. CONCLUSIONS: Increased palm oil consumption is related to higher IHD mortality rates in developing countries. Palm oil consumption represents a saturated fat source relevant for policies aimed at reducing cardiovascular disease burdens.