Packing Returning Secretaries

We study online secretary problems with returns in combinatorial packing domains with $n$ candidates that arrive sequentially over time in random order. The goal is to accept a feasible packing of candidates of maximum total value. In the first variant, each candidate arrives exactly twice. All $2n$ arrivals occur in random order. We propose a simple 0.5-competitive algorithm that can be combined with arbitrary approximation algorithms for the packing domain, even when the total value of candidates is a subadditive function. For bipartite matching, we obtain an algorithm with competitive ratio at least $0.5721 - o(1)$ for growing $n$, and an algorithm with ratio at least $0.5459$ for all $n \ge 1$. We extend all algorithms and ratios to $k \ge 2$ arrivals per candidate. In the second variant, there is a pool of undecided candidates. In each round, a random candidate from the pool arrives. Upon arrival a candidate can be either decided (accept/reject) or postponed (returned into the pool). We mainly focus on minimizing the expected number of postponements when computing an optimal solution. An expected number of $\Theta(n \log n)$ is always sufficient. For matroids, we show that the expected number can be reduced to $O(r \log (n/r))$, where $r \le n/2$ is the minimum of the ranks of matroid and dual matroid. For bipartite matching, we show a bound of $O(r \log n)$, where $r$ is the size of the optimum matching. For general packing, we show a lower bound of $\Omega(n \log \log n)$, even when the size of the optimum is $r = \Theta(\log n)$.Comment: 23 pages, 5 figure

Generic but Expensive: Why Prices Can Remain High for Off-Patent Drugs

Brand-name prescription drugs are sold at extremely high prices in the US because patents and other market exclusivities provided by the government allow manufacturers to exclude direct competition. This period of market exclusivity was intended for pharmaceutical manufacturers to recoup costs associated with research and development of those products and make profits. The other intended outcome of this system is that the market exclusivity period for brand-name drugs should be self-limited, with competition being able to flourish after the market exclusivities end. Such competition has been most effectively supplied by generic drug manufacturers that produce Food and Drug Administration (FDA)-approved bioequivalent versions of the brand-name product. The market entry of these generic drugs—with market uptake augmented by automatic substitution of brand-name prescriptions at the pharmacy— remains the only market intervention that lowers prescription drug prices consistently and substantially. Generic manufacturers can make their drugs available at considerably lower cost because of various market advantages they have over brand-name drugs. When this process does not operate as intended, drug prices do not fall after market exclusivity expiration, or prices for generic drugs may actually increase. In this paper, we examine the variety of factors that mitigate the cost savings associated with introduction of interchangeable generic drugs, especially older, off-patent drugs. We then consider policy solutions that may help stabilize the generic drug marketplace, diminishing the frequency and impact of generic price increases

Strategies and Practices in Off-Label Marketing of Pharmaceuticals: A Retrospective Analysis of Whistleblower Complaints

Aaron Kesselheim and colleagues analyzed unsealed whistleblower complaints against pharmaceutical companies filed in US federal fraud cases that contained allegations of off-label marketing, and develop a taxonomy of the various off-label practices

Use of generic medicines in Latvia : Awareness, opinions and experiences of the population

Funding Information: Funding was provided by EEA Financial Mechanism and Latvian state (award number 2012.EEZ/DAP/MIC/183). The project is financially supported by Iceland, Liechtenstein and Norway. Publisher Copyright: © 2019 The Author(s).Background: To stimulate use of generic medicines a combination of supply and demand side mechanisms are employed in the Latvian reimbursement system. It is reported that patients have high out-of-pocket pharmaceutical spending and that they overpay by not choosing generic medicines. Patient preferences may be an important obstacle in implementing generic policy. Objective of this study was to assess awareness, opinions and experience of the Latvian population regarding use of generic medicines. Methods: Survey of representative sample of the population of Latvia (n = 1005) aged 18-74 was conducted in March 2015. The survey was distributed in Latvian and Russian languages using Computer Assisted Web Interviews. Associations between experience with generic medicines, preference for medicines, and sociodemographic variables were tested with Pearson Chi-square statistics. Associations between the previous experience and information given by different sources versus choice between medicines were tested with Spearman's correlation test. Results: 72.3% of the population were informed about generic medicines. Men (66.9%) and respondents with primary or secondary education (58.3%; 69.3%) were less informed compared to total (72.3%). From those who recalled using generic medicines (n = 441), 94.4% evaluated their experience as positive or neutral. Despite this, only 21% of the population would opt for generic medicines. The strongest preference for brand-name medicines was in the age group > 55 (40.5%). Opinion of a physician was the most important factor when choosing between generic and brand-name medicines (88.7%). The more positive the information provided by general practitioners, physician specialists, pharmacists, family members, friends and internet is perceived, the more likely respondents are to choose generic medicines (p < 0.001). Conclusion: This study demonstrates that people in Latvia are aware of generic medicines but only a minority of the population would choose them when presented with a choice. It is therefore important that health care professionals provide objective and unbiased information about generic medicines to their patients. Interventions should aim to reach groups that are less informed and to improve providers' understanding and communication with patients about generics.publishersversionPeer reviewe

DISPATCH: An Optimally-Competitive Algorithm for Maximum Online Perfect Bipartite Matching with i.i.d. Arrivals

This work presents an optimally-competitive algorithm for the problem of maximum weighted online perfect bipartite matching with i.i.d. arrivals. In this problem, we are given a known set of workers, a distribution over job types, and non-negative utility weights for each pair of worker and job types. At each time step, a job is drawn i.i.d. from the distribution over job types. Upon arrival, the job must be irrevocably assigned to a worker and cannot be dropped. The goal is to maximize the expected sum of utilities after all jobs are assigned. We introduce DISPATCH, a 0.5-competitive, randomized algorithm. We also prove that 0.5-competitive is the best possible. DISPATCH first selects a "preferred worker" and assigns the job to this worker if it is available. The preferred worker is determined based on an optimal solution to a fractional transportation problem. If the preferred worker is not available, DISPATCH randomly selects a worker from the available workers. We show that DISPATCH maintains a uniform distribution over the workers even when the distribution over the job types is non-uniform

Investigating and learning lessons from early experiences of implementing ePrescribing systems into NHS hospitals:a questionnaire study

Background: ePrescribing systems have significant potential to improve the safety and efficiency of healthcare, but they need to be carefully selected and implemented to maximise benefits. Implementations in English hospitals are in the early stages and there is a lack of standards guiding the procurement, functional specifications, and expected benefits. We sought to provide an updated overview of the current picture in relation to implementation of ePrescribing systems, explore existing strategies, and identify early lessons learned.Methods: a descriptive questionnaire-based study, which included closed and free text questions and involved both quantitative and qualitative analysis of the data generated.Results: we obtained responses from 85 of 108 NHS staff (78.7% response rate). At least 6% (n = 10) of the 168 English NHS Trusts have already implemented ePrescribing systems, 2% (n = 4) have no plans of implementing, and 34% (n = 55) are planning to implement with intended rapid implementation timelines driven by high expectations surrounding improved safety and efficiency of care. The majority are unclear as to which system to choose, but integration with existing systems and sophisticated decision support functionality are important decisive factors. Participants highlighted the need for increased guidance in relation to implementation strategy, system choice and standards, as well as the need for top-level management support to adequately resource the project. Although some early benefits were reported by hospitals that had already implemented, the hoped for benefits relating to improved efficiency and cost-savings remain elusive due to a lack of system maturity.Conclusions: whilst few have begun implementation, there is considerable interest in ePrescribing systems with ambitious timelines amongst those hospitals that are planning implementations. In order to ensure maximum chances of realising benefits, there is a need for increased guidance in relation to implementation strategy, system choice and standards, as well as increased financial resources to fund local activitie

Decision making under uncertainty: comparing regulatory and health technology assessment reviews of medicines in the United States and Europe

Assessments of clinical evidence vary between regulators and health technology assessment bodies, but precise differences remain unclear. To compare uncertainties raised on the clinical evidence of approved drugs, we analyzed assessments of regulators and health technology assessment (HTA) bodies in the United States and Europe. We found that US and European regulators report uncertainties related to safety for almost all drugs (85–94%), whereas HTA bodies reported these less (53–59%). By contrast, HTA bodies raised uncertainties related to effects against relevant comparators for almost all drugs (88–100%), whereas this was infrequently addressed by regulators (12–32%). Regulators as well as HTA bodies reported uncertainties related to the patient population for 60–95% of drugs. The patterns of regulator-HTA misalignment were comparable between the United States and Europe. Our results indicate that increased coordination between these complementary organizations is necessary to facilitate the collection of necessary evidence in an efficient and timely manner

Should Research Ethics Encourage the Production of Cost-Effective Interventions?

This project considers whether and how research ethics can contribute to the provision of cost-effective medical interventions. Clinical research ethics represents an underexplored context for the promotion of cost-effectiveness. In particular, although scholars have recently argued that research on less-expensive, less-effective interventions can be ethical, there has been little or no discussion of whether ethical considerations justify curtailing research on more expensive, more effective interventions. Yet considering cost-effectiveness at the research stage can help ensure that scarce resources such as tissue samples or limited subject popula- tions are employed where they do the most good; can support parallel efforts by providers and insurers to promote cost-effectiveness; and can ensure that research has social value and benefits subjects. I discuss and rebut potential objections to the consideration of cost-effectiveness in research, including the difficulty of predicting effectiveness and cost at the research stage, concerns about limitations in cost-effectiveness analysis, and worries about overly limiting researchers’ freedom. I then consider the advantages and disadvantages of having certain participants in the research enterprise, including IRBs, advisory committees, sponsors, investigators, and subjects, consider cost-effectiveness. The project concludes by qualifiedly endorsing the consideration of cost-effectiveness at the research stage. While incorporating cost-effectiveness considerations into the ethical evaluation of human subjects research will not on its own ensure that the health care system realizes cost-effectiveness goals, doing so nonetheless represents an important part of a broader effort to control rising medical costs

The Prevalence and Cost of Unapproved Uses of Top-Selling Orphan Drugs

Introduction: The Orphan Drug Act encourages drug development for rare conditions. However, some orphan drugs become top sellers for unclear reasons. We sought to evaluate the extent and cost of approved and unapproved uses of orphan drugs with the highest unit sales. Methods We assessed prescription patterns for four top-selling orphan drugs: lidocaine patch (Lidoderm) approved for post-herpetic neuralgia, modafinil (Provigil) approved for narcolepsy, cinacalcet (Sensipar) approved for hypercalcemia of parathyroid carcinoma, and imatinib (Gleevec) approved for chronic myelogenous leukemia and gastrointestinal stromal tumor. We pooled patient-specific diagnosis and prescription data from two large US state pharmaceutical benefit programs for the elderly. We analyzed the number of new and total patients using each drug and patterns of reimbursement for approved and unapproved uses. For lidocaine patch, we subcategorized approved prescriptions into two subtypes of unapproved uses: neuropathic pain, for which some evidence of efficacy exists, and non-neuropathic pain. Results: We found that prescriptions for lidocaine patch, modafinil, and cinacalcet associated with non-orphan diagnoses rose at substantially higher rates (average monthly increases in number of patients of 14.6, 1.45, and 1.58) than prescriptions associated with their orphan diagnoses (3.12, 0.24, and 0.03, respectively (p75%). Increases in lidocaine patch use for non-neuropathic pain far exceeded neuropathic pain (10.2 vs. 3.6 patients, p<0.001). Discussion In our sample, three of four top-selling orphan drugs were used more commonly for non-orphan indications. These orphan drugs treated common clinical symptoms (pain and fatigue) or laboratory abnormalities. We should continue to monitor orphan drug use after approval to identify products that come to be widely used for non-FDA approved indications, particularly those without adequate evidence of efficacy