The Case for Preemptive Oligopoly Regulation

One of the few things former President Donald Trump and leading Democrats appear to agree on is the need to subject Big Technology (“Big Tech”) firms to antitrust scrutiny. But unsurprisingly they disagree about how to address the problem. Senator Elizabeth Warren and many other leading Democrats have called for breaking up large technology firms, such as Google, Amazon, and Facebook, in a revival of the trust-busting progressive era of the early twentieth century. In contrast, the Trump administration triggered more traditional antitrust monopoly review of potential anticompetitive activities of a number of leading technology firms, which is more likely to lead to financial sanctions (or more modest consequences). This Article argues that politicians may be identifying a legitimate concern about the market power of actors in highly concentrated markets. But they are looking at the problem through the wrong lens. The larger concern is less monopoly and more oligopoly domination (and more the potential than the current impact of oligopolies on the marketplace). The challenge of oligopolies is that it is difficult to monitor the individual and collective exercise of market power by oligopolists. Existing oligopoly regulation in the United States is almost exclusively reactive and fails to identify and address the potential impact of market concentration with the notable exception of the Federal Trade Commission’s and Department of Justice’s review of prospective mergers. The Article makes the case for creating a mandate for federal regulators to oversee oligopolies in a preemptive way in order to better identify the potential for market abuses and to open up concentrated markets to greater competition. The underlying logic is that even if regulators cannot pinpoint antitrust violations in the present, the higher the degree of market concentration the greater the risk that oligopolies will possess and exercise market power to entrench their power and undercut competition. But rather than focusing on invasive divestments, this Article suggests that policymakers consider employing a range of disclosure rules, regulatory exemptions, and tax incentives to level the playing field for smaller competitors in oligopolistic markets. This Article focuses on the imperative for antitrust oversight of “filtering” or “access oligopolies” who serve as gatekeepers against fraud, data aggregators, and screeners of information and reputation. A small number of oligopolists dominate internet searches, social networking, online shopping, and more traditional spheres of accounting, rating agencies, and investment banking. Participants in these concentrated markets can easily engage in conscious parallelism to mimic one another’s prices and practices because of the homogenous nature of the goods or services they provide. But the defining feature of many of these oligopolists is that they have prioritized market share growth and entrenchment by focusing on economies of scale, network benefits, and barriers to entry, rather than the conventional supracompetitive pricing that monopolists and oligopolists have embraced in the past. In fact, the paradox of many of these filtering intermediaries is that they may even enhance consumer welfare, such as by offering internet searches or messaging for “free” to consumers, while at the same time leveraging their market power to pressure corporate clients to adopt or retain their services. Conventional antitrust regulation focuses on preventing monopolists’ abuse of their market power to distort market pricing. In contrast, antitrust regulation of oligopolies is almost exclusively reactive and limited in scope. Regulators prohibit express collusion among oligopolies and impose limits on their expansion through mergers and acquisitions based on the potential impact on market concentration. But regulators lack the means to remedy the underlying entrenchment of oligopolies and the resulting market distortions when there is no evidence of express communication or circumstantial evidence of agreement among the parties. This Article will suggest that antitrust regulators sustain preemptive periodic oversight of highly concentrated markets (rather than react primarily in response to merger reviews), impose heightened disclosures on oligopolists to facilitate monitoring, and seek to open up these markets to greater competition by lowering the regulatory, disclosure, and tax barriers to entry for small market participants. This approach may not satisfy those echoing politicians’ calls for mandatory divestments, but it is designed to recognize that high levels of market concentration heighten the potential danger of collusion and leveraging of market power by oligopolists

The Case for Contingent Regulatory Sunsets

Cost-benefit analysis is at the core of regulatory impact analysis for every proposed rule or regulation and is designed to be a structural constraint on the administrative state. The challenge is ex ante cost-benefit analysis necessarily rests on many assumptions, and much more information is available about a regulation’s impact after it has been implemented. But ex post cost-benefit analysis is ad hoc and infrequent in spite of efforts by numerous presidential administrations to promote regulatory lookbacks. I propose institutionalizing “contingent regulatory sunsets” to ensure that rules and regulations have the positive impact in practice that administrative agencies intended. I show how Congress can consider a spectrum of approaches for independent actors to conduct regulatory lookbacks of economically significant regulations at regular intervals. I explore the merits for centralized legislative branch review (Government Accountability Office), strengthened executive branch review (Office of Information and Regulatory Affairs), agencies themselves, and the creation of a new “Regulatory Lookback” agency to take on this role. While each approach has virtues, I conclude that each agency’s Office of Inspector General (OIG) may be best positioned to build on existing oversight functions to provide periodic review of the impact of regulations. If the OIG’s cost-benefit analysis shows that the regulation’s real-world impact is actually negative, then the agency that issued the rule would face the burden of rescinding, modifying, or providing updated justifications and cost-benefit analysis. The goal is not to cripple the workings of the vast administrative state, but rather to provide systematic, internal accountability. The hope is that overly optimistic assumptions about costs and benefits will be tempered by routine ex post scrutiny and the sunlight of empirical reality. I then lay out quantitative and qualitative limiting principles to show how periodic cost-benefit review of economically significant regulations could be economically and politically feasible. I conclude by proposing a pilot study to measure the efficacy of OIG ex post review of regulations to provide evidence to justify expanding this initiative on an executive branch-wide basis

Developing a Set of Core Outcomes for Trials in Haemodialysis: An International Delphi Survey

AIM: To generate a consensus-based, prioritized list of core outcomes for trials in haemodialysis. BACKGROUND: Survival and quality of life for patients on haemodialysis remain poor despite substantial research efforts. Existing trials often report surrogate outcomes that may not be relevant to patients and clinicians. A core outcome set that reflects stakeholder priorities would improve the relevance, efficiency, and comparability of haemodialysis trials. METHODS: In an online Delphi survey, participants rated the importance of outcomes using a 9-point Likert scale. In Round 2 and 3, participants reviewed the scores and comments of other respondents and re-rated the outcomes. For each outcome, we calculated the median, mean, and proportion rating 7-9 (“critically important”). RESULTS: 1,181 participants (202 [17%] patients/caregivers, 979 health professionals) from 73 countries completed Round 1 and 838 (150 [18%] patients/caregivers) completed Round 3 (71% response rate). Outcomes achieving consensus as high priorities across both groups were: vascular access complications, cardiovascular disease, mortality, dialysis adequacy and fatigue. Patients/caregivers rated four outcomes higher than health professionals: ability to travel (mean difference 0.9), dialysis-free time (0.5), dialysis adequacy (0.3), and washed out after dialysis (0.2). Health professionals rated 11 outcomes higher: mortality (1.0), hospitalization (1.0), drop in blood pressure (1.0), vascular access complications (0.9), depression (0.9), cardiovascular disease (0.8), target weight (0.7), infection (0.4), potassium (0.4), ability to work (0.3), and pain (0.3). CONCLUSIONS: The top stakeholder prioritized outcomes were vascular access problems, cardiovascular disease, mortality, dialysis adequacy and fatigue. Patients/caregivers gave higher priority to lifestyle-related outcomes than health professionals. This prioritized set of outcomes can inform the establishment of a core outcome set, to improve the value of trial evidence to support decision-making for people on haemodialysis

Standardized Outcomes in Nephrology-Transplantation: A Global Initiative to Develop a Core Outcome Set for Trials in Kidney Transplantation.

BACKGROUND: Although advances in treatment have dramatically improved short-term graft survival and acute rejection in kidney transplant recipients, long-term graft outcomes have not substantially improved. Transplant recipients also have a considerably increased risk of cancer, cardiovascular disease, diabetes, and infection, which all contribute to appreciable morbidity and premature mortality. Many trials in kidney transplantation are short-term, frequently use unvalidated surrogate endpoints, outcomes of uncertain relevance to patients and clinicians, and do not consistently measure and report key outcomes like death, graft loss, graft function, and adverse effects of therapy. This diminishes the value of trials in supporting treatment decisions that require individual-level multiple tradeoffs between graft survival and the risk of side effects, adverse events, and mortality. The Standardized Outcomes in Nephrology-Transplantation initiative aims to develop a core outcome set for trials in kidney transplantation that is based on the shared priorities of all stakeholders. METHODS: This will include a systematic review to identify outcomes reported in randomized trials, a Delphi survey with an international multistakeholder panel (patients, caregivers, clinicians, researchers, policy makers, members from industry) to develop a consensus-based prioritized list of outcome domains and a consensus workshop to review and finalize the core outcome set for trials in kidney transplantation. CONCLUSIONS: Developing and implementing a core outcome set to be reported, at a minimum, in all kidney transplantation trials will improve the transparency, quality, and relevance of research; to enable kidney transplant recipients and their clinicians to make better-informed treatment decisions for improved patient outcomes

Sleep-wake sensitive mechanisms of adenosine release in the basal forebrain of rodents : an in vitro study

Adenosine acting in the basal forebrain is a key mediator of sleep homeostasis. Extracellular adenosine concentrations increase during wakefulness, especially during prolonged wakefulness and lead to increased sleep pressure and subsequent rebound sleep. The release of endogenous adenosine during the sleep-wake cycle has mainly been studied in vivo with microdialysis techniques. The biochemical changes that accompany sleep-wake status may be preserved in vitro. We have therefore used adenosine-sensitive biosensors in slices of the basal forebrain (BFB) to study both depolarization-evoked adenosine release and the steady state adenosine tone in rats, mice and hamsters. Adenosine release was evoked by high K+, AMPA, NMDA and mGlu receptor agonists, but not by other transmitters associated with wakefulness such as orexin, histamine or neurotensin. Evoked and basal adenosine release in the BFB in vitro exhibited three key features: the magnitude of each varied systematically with the diurnal time at which the animal was sacrificed; sleep deprivation prior to sacrifice greatly increased both evoked adenosine release and the basal tone; and the enhancement of evoked adenosine release and basal tone resulting from sleep deprivation was reversed by the inducible nitric oxide synthase (iNOS) inhibitor, 1400 W. These data indicate that characteristics of adenosine release recorded in the BFB in vitro reflect those that have been linked in vivo to the homeostatic control of sleep. Our results provide methodologically independent support for a key role for induction of iNOS as a trigger for enhanced adenosine release following sleep deprivation and suggest that this induction may constitute a biochemical memory of this state

IL28B genotype is associated with cirrhosis or transition to cirrhosis in treatment-naive patients with chronic HCV genotype 1 infection: the international observational Gen-C study

Background and purpose: Contradictory data exist on the association between host interleukin-28B (IL28B) rs12979860 genotype and liver fibrosis in patients with chronic hepatitis C (CHC). This large, international, observational study (NCT01675427/MV25600) investigated relationships between IL28B rs12979860 genotype and liver fibrosis stage in CHC patients. Methods: A total of 3003 adult, treatment-naive CHC patients were enrolled into the study. Patients made one study visit to provide a blood sample for genotyping; other data were obtained from medical records. Results: 2916 patients comprised the analysis population; the majority were enrolled in Europe (n = 2119), were Caucasian (n = 2582) and had hepatitis C virus (HCV) genotype (G) 1 infection (n = 1702) (G2 = 323, G3 = 574, G4 = 260). Distribution of IL28B genotypes varied according to region of enrolment, patient ethnicity and HCV genotype. A significant association was observed between increasing number of IL28B T alleles and the prevalence of cirrhosis/transition to cirrhosis (based on biopsy or non-invasive assessments) in G1-infected patients (CC = 22.2% [111/499], CT = 27.5% [255/928], TT = 32.3% [87/269]; p = 0.0018). The association was significant in the large subgroup of European Caucasian G1 patients (n = 1245) but not in the smaller Asian (n = 25), Latin American (n = 137) or Middle Eastern (n = 289) G1 subgroups. IL28B genotype was not associated with liver fibrosis stage in patients with HCV G2, G3 or G4 infection. Conclusion: This large, international study found that IL28B rs12979860 genotype is significantly associated with liver fibrosis stage in CHC patients with HCV G1 infection. This association was evident in European Caucasians but not in G1-infected patients from Asia, Latin America or the Middle EastF. Hoffmann-La Roche Ltd, Basel, Switzerlan

Differential adherence and expression of virulence traits by Candida albicans and Candida parapsilosis in mono- and dual-species cultures in artificial saliva

AIMS: To evaluate specific virulence factors of Candida albicans and Candida parapsilosis clinical oral isolates in mono- and dual-species culture in the presence of artificial saliva. METHODS AND RESULTS: Two of the strains used in this study were isolated from co-infection (C. albicans AM and C. parapsilosis AM2), and the other two were isolated from single infection (C. albicans AC and C. parapsilosis AD). The number of adhered yeast cells was measured and their enzymatic activity was determined simultaneously. In mono-species culture, C. parapsilosis strains adhered to a higher extent to the surface in comparison with the C. albicans strains. In dual-species culture, the C. parapsilosis strains adhered more in the presence of C. albicans AM. Interestingly, C. albicans AM and C. parapsilosis AD adhered to a higher extent when compared with all other co-cultures. In dual-species culture, the enzymatic activity of C. parapsilosis strains in the presence of C. albicans AC was higher than in the presence of C. albicans AM. CONCLUSIONS: The virulence factors of C. albicans and C. parapsilosis differ from strain to strain and are influenced by the presence of other species in culture. SIGNIFICANCE AND IMPACT OF THE STUDY: To understand the expression of virulence factors in Candida dual-species systems.This work was supported by Portuguese Foundation for Science and Technology (FCT) through the grant SFRH/BPD/20987/2004 attributed to Claudia Botelho

Establishing Core Outcome Domains in Hemodialysis: Report of the Standardized Outcomes in Nephrology-Hemodialysis (SONG-HD) Consensus Workshop

Evidence-informed decision making in clinical care and policy in nephrology is undermined by trials that selectively report a large number of heterogeneous outcomes, many of which are not patient centered. The Standardized Outcomes in Nephrology-Hemodialysis (SONG-HD) Initiative convened an international consensus workshop on November 7, 2015, to discuss the identification and implementation of a potential core outcome set for all trials in hemodialysis. The purpose of this article is to report qualitative analyses of the workshop discussions, describing the key aspects to consider when establishing core outcomes in trials involving patients on hemodialysis therapy. Key stakeholders including 8 patients/caregivers and 47 health professionals (nephrologists, policymakers, industry, and researchers) attended the workshop. Attendees suggested that identifying core outcomes required equitable stakeholder engagement to ensure relevance across patient populations, flexibility to consider evolving priorities over time, deconstruction of language and meaning for conceptual consistency and clarity, understanding of potential overlap and associations between outcomes, and an assessment of applicability to the range of interventions in hemodialysis. For implementation, they proposed that core outcomes must have simple, inexpensive, and validated outcome measures that could be used in clinical care (quality indicators) and trials (including pragmatic trials) and endorsement by regulatory agencies. Integrating these recommendations may foster acceptance and optimize the uptake and translation of core outcomes in hemodialysis, leading to more informative research, for better treatment and improved patient outcomes