High-priced medications with curative potential, such as the newer hepatitis C therapies, have contributed to the recent growth in pharmaceutical expenditure. Despite the obvious benefits, health ...care decision makers are just beginning to grapple with questions of how to value and pay for curative therapies that may feature large upfront cost, followed by health benefits that are reaped over a patient's lifespan. Alternative policy options have been proposed to promote high value and financially sustainable use of these therapies. It is unclear which policy options would be most acceptable to health care payer and biomedical manufacturer stakeholders.
To (a) briefly review pharmaceutical policy options to address health system affordability and (b) assess the acceptability of alternative policy options to health care payers and biomedical manufacturers before and after an Academy of Managed Care Pharmacy (AMCP) continuing pharmacy education (CPE) session.
We searched MEDLINE and Cochran databases for pharmaceutical policy options addressing affordability. With input from a focus group of managed care professionals, we developed CPE session content and an 8-question survey focusing on the most promising policy options. We fielded the survey before and after the CPE session, which occurred as part of the 2016 AMCP Annual Meeting. We first conducted a chi-squared goodness-of-fit test to assess response distributions. Next, we tested how responses differed before and after by using an ordered logit and a multinomial logit to model Likert scale and unordered responses, respectively.
Although risk-sharing payments over time remained the most favorable choice before (37%) and after (35%) the CPE session, this choice was closely followed by HealthCoin after the session, which increased in favorability from 4% to 33% of responses (P = 0.001). About half of the respondents (54%) indicated that legislative change is the most significant barrier to the implementation of any policy.
As high-cost curative drugs reach the market, managed care stakeholders need information from a balanced education source regarding alternative policies to address affordability. We found that after the AMCP CPE session, risk-sharing payments over time and HealthCoin were the most favorable options.
No funding was provided for this research. Carlson reports consulting fees from Genentech, Pfizer, and Seattle Genetics. The other authors have nothing to disclose. Study concept and design were contributed by Yeung, Garrison, and Carlson. Yeung collected the data, which were interpreted by Yeung and Basu. The manuscript was written by Yeung, Suh, and Bansal and revised by Yeung. A portion of this research was presented at the Academy of Managed Care & Specialty Pharmacy Annual Meeting as a continuing education session entitled "Paying for Cures: How Can We Afford It?" on April 20, 2016, in San Francisco, California.
Activated platelets release cytokines/proteins including CXCL4 (PF4), CCL5 and fibrinopeptides, which regulate infection of several pathogenic viruses such as HIV, H1N1 and HCV in human. Since ...platelet activation is the hallmark of Dengue virus (DV) infection, we investigated the role of platelets in DV replication and also in a closely related Japanese Encephalitis virus (JEV).
Microscopy and PCR analysis revealed a 4-fold increase in DV replication in primary monocytes or monocytic THP-1 cells in vitro upon incubation with either DV-activated platelets or supernatant from DV-activated platelets. The mass spectrometry based proteomic data from extra-nuclear fraction of above THP-1 lysate showed the crucial association of PF4 with enhanced DV replication. Our cytokine analysis and immunoblot assay showed significant inhibition of IFN-α production in monocytes via p38MAPK-STAT2-IRF9 axis. Blocking PF4 through antibodies or its receptor CXCR3 through inhibitor i.e. AMG487, significantly rescued production of IFN-α resulting in potent inhibition of DV replication in monocytes. Further, flow cytometry and ELISA data showed the direct correlation between elevated plasma PF4 with increased viral NS1 in circulating monocytes in febrile DV patients at day-3 of fever than day-9. Similarly, PF4 also showed direct effects in promoting the JEV replication in monocytes and microglia cells in vitro. The in vitro results were also validated in mice, where AMG487 treatment significantly improved the survival of JEV infected animals. Interpretation: Our study suggests that PF4-CXCR3-IFN axis is a potential target for developing treatment regimen against viral infections including JEV and DV.
Comparative effectiveness research (CER) can provide valuable information for patients, providers and payers. These stakeholders differ in their incentives to invest in CER. To maximize benefits from ...public investments in CER, it is important to understand the value of CER from the perspectives of these stakeholders and how that affects their incentives to invest in CER. This article provides a conceptual framework for valuing CER, and illustrates the potential benefits of such studies from a number of perspectives using several case studies.We examine cases in which CER provides value by identifying when one treatment is consistently better than others, when different treatments are preferred for different subgroups, and when differences are small enough that decisions can be made based on price. We illustrate these findings using value-of-information techniques to assess the value of research, and by examining changes in pharmaceutical prices following publication of a comparative effectiveness study.Our results suggest that CER may have high societal value but limited private return to providers or payers. This suggests the importance of public efforts to promote the production of CER. We also conclude that value-of-information toolsmay help inform policy decisions about how much public funds to invest in CER and how to prioritize the use of available public funds forCER, in particular targeting publicCERspending to areas where private incentives are low relative to social benefits.
Objective. To examine the effect of Part D on 65–78‐year‐old noninstitutionalized dual eligibles' prescription utilization and expenditures.
Data Source. Random sample of unique pharmacy customers of ...a national retail pharmacy chain who filled at least one prescription during both 2005 and 2006. For each subject, we obtained claims data for every prescription filled between January 1, 2005, and April 31, 2007.
Study Design. Generalized estimating equations were used to examine the experience of a “treatment” group (dual eligibles between 65 and 78 years on January 1, 2005) with that of a “control” group (near‐elderly patients with Medicaid coverage between 60 and 63 years on January 1, 2005) during the first 18 months after Part D implementation.
Principal Findings. Expenditures for the treatment and control groups tracked each other closely in the pre–Part D period. Immediately following the implementation of Part D, expenditures for both groups decreased and then leveled off. There were no significant changes in trends in the dual eligibles' out‐of‐pocket expenditures, total monthly expenditures, pill‐days, or total number of prescriptions due to Part D.
Conclusions. We find no evidence that Part D adversely affected pharmaceutical utilization or out‐of‐pocket expenditures of dual eligibles during the transition period, nor during the 16 months subsequent to Part D implementation.
Objective. Value of information (VOI) analyses can align research with areas with the greatest potential impact on patient outcome, but questions remain concerning the feasibility and acceptability ...of these approaches to inform prioritization decisions. Our objective was to develop a process for calculating VOI in “real time” to inform trial funding decisions within SWOG, a large cancer clinical trials group. Methods. We developed an efficient and scalable VOI modeling approach using a selected sample of 9 randomized phase II/III trial proposals from the Breast, Gastrointestinal, and Genitourinary Disease Committees reviewed by SWOG’s leadership between 2008 and 2013. There was bidirectional communication between SWOG investigators and the research team throughout the modeling development. Partial expected value of sample information for the treatment effect evaluated by the proposed trial’s primary endpoint was calculated using Monte Carlo simulation. Results. We derived prior uncertainty in the treatment effect estimate from the sample size calculations. Our process was feasible for 8 of 9 trial proposals and efficient: the time required of 1 researcher was <1 week per proposal. We accommodated stakeholder input primarily by deconstructing VOI metrics into expected health benefits and incremental healthcare costs and assuming treatment decisions within our simulations were based on health benefits. Following customization, feedback from over 200 SWOG members was positive regarding the overall VOI framework, specific retrospective results, and potential for VOI analyses to inform future trial proposal evaluations. Conclusions. We developed an efficient and customized process to calculate the expected VOI of cancer clinical trials that is feasible for use in decision making and acceptable to investigators. Prospective use and evaluation of this approach is currently underway within SWOG.
In Ciphertext Policy Attribute-Based Encryption (CP-ABE) system, a set of attributes is associated with the private keys of each user. Also, the ciphertext is attached with a policy which is defined ...over that set of attributes. A user can decrypt the ciphertext if the ciphertext’s policy is satisfied by the attributes associated hith her private key. Traditional CP-ABE schemes, based on number theoretic problems, rely on a trustworthy central authority. But in many distributed applications it is expected that such authorities should be decentralized to avoid the risks of single-point failure. While the number theory-based hardness problems are prone to quantum attacks, lattice-based hardness problems can resist such attacks. In this paper, we construct a Decentralized Ciphertext-Policy Attribute-Based Encryption (DCP-ABE) scheme. Under this scheme, any participating entity can act as an authority by creating a public key. The athority utilizes the users’ attributes to generate the private keys for them. Any user can encrypt data in terms of any monotone access structure over attributes issued from any chosen set of authorities. Hence the protocol does not depend on any central authority. We utilize Learning With Errors over Rings (R-LWE) as the underlying hardness assumption for te protocol. The proposed post-quantum protocol achieves security under selective-set model whereby adversaries are allowed to corrupt any authority only statically through adaptive key queries.
Background
Sickle cell disease (SCD) is a complex genetic disorder that manifests in infancy and progresses throughout life in the form of acute and chronic complications. As the upfront costs of ...potentially curative, genetic therapies will likely be high, an assessment and comprehensive characterization of the medical and non-medical cost burden will inform future decision making.
Objective
We sought to systematically summarize the existing literature surrounding SCD medical and non-medical costs.
Methods
We searched MEDLINE and EMBASE (2008–2020) and identified US-based studies that detailed medical or non-medical costs. Eligible studies provided empirical estimates about any aspect of cost or SCD individuals of all ages and their caregivers. Study quality was assessed using the Newcastle–Ottawa Scale, and costs were adjusted to 2019 US$.
Results
Search queries returned 479 studies, with 342 from medical burden searches and 137 from non-medical burden searches, respectively. Herein, we report the results of the 40 studies that contained relevant cost information: 39 detailed medical costs and 1 detailed non-medical costs. Costs were higher for SCD patients when compared with non-SCD individuals (cost difference range: $6636–$63,436 annually). The highest medical cost component for SCD patients was inpatient ($11,978–$59,851 annually), followed by outpatient and then pharmacy. No studies characterized the cost burden throughout the lifetime disease trajectory of an SCD individual, and no studies captured caregiver or productivity costs.
Conclusion
Our results reveal an incomplete characterization of medical and non-medical costs within SCD. A deeper understanding of the medical and non-medical cost burden requires completion of additional studies that capture the burden across the patient’s lifetime, in addition to expression of the impact of existing and emergent health technologies on disease trajectory.
4-Methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK) is a tobacco-specific procarcinogen. We have investigated whether NNK causes inflammatory upheaval in the brain by activation of resident microglia ...and astrocyte and result in bystander neuronal damage. We have carried out the work in both in vitro and in vivo models. We have found that treatment with NNK causes significant activation of mouse microglial (BV2) cell line as evident by increase in reactive oxygen species and nitric oxide level. Western blot analysis has showed increase in proinflammatory signaling proteins, proinflammatory effector proteins, and other stress-related proteins. Interestingly, increased levels of proinflammatory cytokines like interleukin (IL)-6, tumor necrosis factor-α, monocyte chemoattractant protein 1 (MCP1), and IL-12p70 are also detected. Work from our in vivo studies has demonstrated similar increase in proinflammatory signaling and effector molecules along with the proinflammatory cytokine levels, following NNK treatment. Immunohistochemical staining of the brain sections of NNK-treated mice reveals massive microglial and astrocyte activation along with distinct foci of neuronal damage. Both in vitro and in vivo results provide strong indication that NNK causes significant upheaval of the inflammatory condition of brain and inflicts subsequent neuronal damage.
We consider some string invariants at genus two that appear in the analysis of the \(D^8\mathcal{R}^4\) and \(D^6\mathcal{R}^5\) interactions in type II string theory. We conjecture a Poisson ...equation involving them and the Kawazumi--Zhang invariant based on their asymptotic expansions around the non--separating node in the moduli space of genus two Riemann surfaces.
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