Navarro is a clinical professor in the College of Pharmacy at the University of Florida, Gainesville, and is an assistant editor with the Journal of Managed Care and Specialty Pharmacy. Navarro ...reports consulting fees from Analysis Group, Amgen, Novartis, and Allergan.
Outcomes-based contracts (OBCs), a type of risk-sharing arrangement (RSA), have emerged as a promising avenue for payers to engage with pharmaceutical manufacturers to share risk and improve patient ...access to medicines via evaluation of real-world outcomes.
To assess the level of recent OBC activity and stakeholder perceptions of these arrangements, as well as the outlook for future OBC activity from a payer and manufacturer perspective in the United States and EU-5 (France, Germany, Italy, Spain, and the United Kingdom).
Using a structured questionnaire, interviews were conducted with 27 experts, including 14 U.S. payers, 5 EU-5 national payers, and 8 manufacturer pricing/market access executives (4 U.S., 4 EU-5). We also used the University of Washington's Performance Based Risk-Sharing (PBRS) database and other targeted publicly available information.
Publicly disclosed information on OBCs understates the level of OBC activity, since many arrangements are confidential. Overall, U.S. and EU-5 interviewees generally expected that 2 to 3 times more OBCs would be implemented in the next 5 years than in the previous 5 years. Key drivers included the introduction of a national OBC framework in Spain, potentially a similar framework in the United Kingdom, a growing sickness fund activity in Germany, and a U.S. movement towards accountable care. Motivation for OBCs varied markedly across markets and stakeholders, with operational feasibility noted as a significant hurdle in the United States and France. Along with improving health outcomes, cost and financial risk reduction were the primary OBC motivators for payers, while potential access or reimbursement gains were key factors for manufacturers.
Using direct input from U.S. and EU-5 payer and pharmaceutical manufacturer decision makers, this research suggests that high OBC growth is expected in the EU-5 and, to a more moderate extent, in the United States, particularly if clear, simpler OBC frameworks can be developed.
This study was funded by Novartis Pharmaceuticals. Novartis employees were involved in all aspects of this study. Vegesna and Sasane are employed by and own stock in Novartis. Nazareth and Ko were employees of Novartis at the time of this study. Frois, Demean, Carpenter, and Wu are or have been employed by Analysis Group, which received a grant from Novartis for this research. Navarro received consulting fees from Novartis for his involvement in this research. Study concept and design were contributed by Sasane, Frois, Nazareth, and Wu. Navarro, Demean, and Frois took the lead in data collection, assisted by Carpenter, Ko, and Nazareth. Data interpretation was provided by Frois, Carpenter, Nazareth, and Ko, along with Sasane, Demean, Wu, and Navarro. The manuscript was written by Frois, Demean, Nazareth, and Ko, along with Sasane, Carpenter, Wu, and Navarro, and revised by Frois, Ko, and Vegesna, along with Sasane, Nazareth, Wu, and Navarro.
Formulary management within a limited budget is critical, especially for specialty drugs, which are used for serious medical conditions and are very expensive. Despite attempts to summarize the ...pertinent evidence, it is uncertain whether data needs of formulary decision makers for specialty drugs are satisfied.
To assess the level of satisfaction of specialty drug formulary decision makers with regards to the strength of current available data sources and unmet needs regarding clinical, economic, and unpublished evidence.
This study targeted pharmacists and physicians involved with formulary decision making at health plans or pharmacy benefit management companies at the national, large regional, and local levels. 95 individuals were invited to participate (without compensation) in a 21-item, web-based survey (Qualtrics), which was open from June 14 to July 31, 2014. The responses were coded for descriptive and statistical analysis. Statistical analyses included the Kruskal-Wallis test, analysis of variance, and the Mann-Whitney-Wilcoxon test.
Of 95 pharmacists or physicians, 40 respondents initiated the survey, and 33 respondents completed the survey (response rate = 34.7%). Drug formulary decision makers infrequently rated data evidence strength (17.1% "always"). Clinical data evidence strength was rated highest with published randomized controlled trials (RCTs; mean SD = 4.06 0.87 of 5.0), while participant organizations' internal data were rated highest for economic data evidence strength (mean SD = 3.91 1.07 of 5.0). Decision makers rated the highest unmet need as more data generated from head-to-head RCTs (mean SD = 2.94 0.25 of 3.0) and cost-effectiveness analyses (mean SD = 2.53 0.67 of 3.0). The participants believed manufacturers might be in the best position to satisfy their desire for head-to-head RCTs (mean SD = 4.31 1.09 of 5.0).
Despite a variety of data sources, drug formulary decision makers continue to rely on published RCTs or internal economic analyses as having the strongest evidence strength. The study respondents believed that pharmaceutical manufacturers would be best able to satisfy the greatest clinical data unmet need, that is, head-to-head RCTs in specialty drug formulary decisions.
This study was not funded by any company or pharmaceutical manufacturer. Navarro has worked as a consultant for Biogen, Purdue Pharma, and Novartis and has offered expert testimony on behalf of AstraZeneca. The authors declare no other potential conflicts of interest. Study design was contributed primarily by Navarro, along with Choi. Choi took the lead in data collection and interpretation, assisted by Navarro. Both authors contributed equally to manuscript writing and revision.
As a result of global concern about rising drug costs, many U.S. payers and European agencies such as the National Health Service have partnered with pharmaceutical companies in performance-based ...risk-sharing arrangements (PBRSAs) by which manufacturers share financial risk with health care purchasing entities and authorities. However, PBRSAs present many administrative and legal challenges that have minimized successful contract experiences in the United States.
To (a) identify drug and disease characteristics and contract components that contribute to successful PBRSA experiences and the primary barriers to PBRSA execution and (b) explore solutions to facilitate contract negotiation and execution.
A 37-item, web-based survey instrument (Qualtrics), approximately 20 minutes in duration, was open during July and August 2016. The survey was emailed to 90 pharmacy and medical directors of various health care organizations. Statistical analysis included the Kruskal-Wallis test and chi-square tests to examine differences among payer responses. Survey responses were anonymized and data were aggregated.
Twenty-seven individuals completed the survey (30% completion rate). The majority of respondents worked for regional health plans (52%, n = 14), covering at least 1 million lives (63%, n = 17), with at least 7 years of managed care experience (81%, n = 22). A total of 51 PBRSAs were active among respondents at the time of the survey. Easily obtainable and evaluable drug data and medical data were the most important drug and disease attributes for successful PBRSAs, respectively. Pharmacy claims and patient demographic data were assessed as "very easy and inexpensive" to collect. Type and amount of manufacturer payment for drug outcome performance failure, endpoint measurement, and necessary clinical data for drug performance measurement were all critical factors for successful PBRSAs. Standardized contract templates and transparent contract financial risk evaluation and modeling ranked highest among methods of manufacturer facilitation of PBRSAs. This study was limited by sample size and survey questions were limited to explanation of PBRSAs at the disease state level.
On the basis of PBRSA experiences, respondents noted that drug use in chronic medical conditions and objective drug outcome performance measurements were favorable drug characteristics and serve as the primary source of satisfaction for these types of contracts. Third parties and manufacturers can facilitate the uptake and success of PBRSAs by developing standardized contracting templates in addition to other methods that increase their stake in the arrangement. Looking forward, mounting perceptions of success in this realm of contracting for pharmaceuticals may contribute in the quest for value-based payments in the U.S. health care system.
The construction of the survey and payment for survey respondents were supported by Charles River Associates. Parece is an employee of Charles River Associates. Goble and Ung are completing fellowship training sponsored by Novartis and Celgene, respectively, but do not have any conflicts of interest and did not receive any funding related to this study. Navarro reports consulting fees from Analysis Group, TEVA, and Amgen, unrelated to this study. Van Boemmel-Wegmann declares no conflict of interest. Study concept and design were contributed by Navarro, Goble, Ung, and Parece. Navarro took the lead in data collection, along with Goble and Ung, and data interpretation was performed by van Boemmel-Wegmann, Goble, and Ung. The manuscript was written by Goble, Ung, Navarro, and van Boemmel-Wegmann and revised by all of the authors.
Shiga toxin-producing
(STEC) are a subset of pathogens leading to illnesses such as diarrhea, hemolytic uremic syndrome and even death. The Shiga toxins are the main virulence factors and divided in ...two groups: Stx1 and Stx2, of which the latter is more frequently associated with severe pathologies in humans.
An immune library of nanobodies (Nbs) was constructed after immunizing an alpaca with recombinant Shiga toxin-2a B subunit (rStx2aB), to retrieve multiple rStx2aB-specific Nbs. The specificity of five Nbs towards rStx2aB was confirmed in ELISA and Western blot. Nb113 had the highest affinity (9.6 nM) and its bivalent construct exhibited a 100-fold higher functional affinity. The structure of the Nb113 in complex with rStx2aB was determined via X-ray crystallography. The crystal structure of the Nb113-rStx2aB complex revealed that five copies of Nb113 bind to the rStx2aB pentamer and that the Nb113 epitope overlaps with the Gb3 binding site, thereby providing a structural basis for the neutralization of Stx2a by Nb113 that was observed on Vero cells. Finally, the tandem-repeated, bivalent Nb113₂ exhibits a higher toxin neutralization capacity compared to monovalent Nb113.
The Nb of highest affinity for rStx2aB is also the best Stx2a and Stx2c toxin neutralizing Nb, especially in a bivalent format. This lead Nb neutralizes Stx2a by competing for the Gb3 receptor. The fusion of the bivalent Nb113₂ with a serum albumin specific Nb is expected to combine high toxin neutralization potential with prolonged blood circulation.
Current cancer therapeutics suffer from a lack of specificity in targeting tumor cells and cause severe side effects. Therefore, the design of highly specialized drugs comprising antibody derivatives ...inducing apoptosis in targeted cancer cells is considered to be a promising strategy. Drugs acting on death receptor 5 (DR5) such as DR5 agonist antibodies replacing "TNF-related apoptosis-inducing ligand" (TRAIL) offer feasible opportunities in this direction. Although such agonists provided good antitumor activity in preclinical studies, they were less effective in clinical studies, possibly due to a disturbed Fc interaction with Fc-γ receptors. Thus, multimerized antigen binding fragments without Fc have been proposed to increase their efficacy. We generated nanobodies (Nbs), recombinant variable domains of heavy chain-only antibodies of camelids, against the DR5 ectodomain. Nb24 and Nb28 had an affinity in the nM and sub-nM range, but only Nb28 competes with TRAIL for binding to DR5. Bivalent, trivalent, and tetravalent constructs were generated, as well as an innovative pentameric Nb complex, to provoke avidity effects. In our cellular assays, these trimeric, tetrameric, and pentameric Nbs have a higher apoptotic capacity than monomeric Nbs and seem to mimic the activity of the natural TRAIL ligand on various cancer cells.
There is no consensus on how to share patient records privately. Data privacy concepts are surveyed and a framework is presented for the safe sharing of sensitive data. It is argued that tailoring ...the data sharing to the privacy breach risks of each project holds out the best compromise for keeping the trust of the public and providing for the best quality data where detailed patient consent is not possible.
To improve the protection of data by reducing privacy breaches and thus enable appropriate patient data sharing without consent.
Any harm arising from data sharing must come from the data being identified, either fully or partially. The first step is an agreement on an acceptable privacy breach risk. Next, proceed to measure that risk for the proposed data when held by a given recipient. Finally, select from a menu of mitigation strategies (people, process and technical) to achieve acceptable risk. The framework is tested against the current UK approach administered by the Patient Information Advisory Group.
The hard problem of non-consented data sharing should be divided into the easier (though non-trivial) ones of data and recipient breach risk measurement. Directed research in these two areas will help move the data sharing problem into the 'solved' pile.
Immunoglobulins are large Y-shaped proteins produced by B-cells and plasma cells that are used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. ...Immunoglobulin G (IgG) preparations are approved by the US Food and Drug Administration for the treatment of primary immunodeficiency disease, idiopathic thrombocytopenic purpura, Kawasaki disease, chronic lymphocytic leukemia with frequent infections, bone marrow transplantation, to prevent infection in pediatric human immunodeficiency virus, and chronic inflammatory demyelinating polyneuropathy. However, IgG products are frequently used off label in many autoimmune conditions. The advent of numerous intravenous and subcutaneous formulations of IgG presents new opportunities impacting patient preferences, site of care, and costs. The appropriate and optimal use of IgG is reviewed based on discussions from an expert roundtable panel and review of the scientific literature. Clinicians and payers should consider patient preferences, evidence- based guidelines, and policies when selecting an IgG product.
A roundtable meeting that comprised clinical, patient advocacy, and managed care experts discussed issues regarding the diagnosis and management of fibromyalgia. The panel agreed that earlier ...diagnosis and treatment, additional education for the medical community, and appropriate management by health plans, including patient access to US Food and Drug Administration-approved fibromyalgia medications, are needed. In addition, physicians, payers, and patient advocates must work to improve clinical, economic, and quality-of-life outcomes for fibromyalgia patients. Finally, treatment and diagnostic guidelines must be updated as advances in disease management are made (including approvals of 3 new pharmacologic agents), and development of a therapeutic category for "fibromyalgia" on payer formularies is needed.
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