The Cost Effectiveness of Two New Antiepileptic Therapies in the Absence of Direct Comparative Data: A First Approximation

Background: A number of new antiepileptic agents have been introduced within a short period of time. Direct comparisons are not available, and information about the balance between costs and effects for these new therapies is lacking. Objective: To introduce a first approximation of the cost effectiveness of the new therapeutic agents (topiramate and lamotrigine) for epilepsy that have been assessed in clinical trials against placebo. Methods: Without head to head comparative data no formal methods are available to assess the relative cost effectiveness of two products; therefore, a Bayesian approach was developed. The approach starts with the `proportionality assumption' saying that the differences in healthcare expenditure (less the direct cost of therapy) are directly proportional to the differences in effectiveness. Given this assumption, a therapy that is x times as expensive as an alternative therapy has an equivalent cost-effectiveness profile if the acquisition cost is x times as high. Moreover, simple formulas can be derived to calculate the probabilities that a therapy is dominant (more effective and less expensive) and that it is weakly dominant (more effective and a better cost-effectiveness profile). The approach is applied to data from published fixed dosage, parallel-design studies comparing both topiramate and lamotrigine with placebo. Results: Assuming that the `proportionality assumption' holds for the medical treatment of epilepsy, and disregarding uncertainties, it is estimated that topiramate may be priced more than 2.2 times its current acquisition cost and still be more cost effective than lamotrigine. Taking uncertainties into account, it is estimated that lamotrigine 500 mg/day is dominated by topiramate 200 mg/day with a probability of 0.875 and by topiramate 400 mg/day with a probability of 0.986. Conclusions: A simple method can be applied to assess the relative cost effectiveness of two therapies in the absence of direct comparative data. Applying this method to compare topiramate and lamotrigine leads to a strong preference for topiramate. However, to be able to draw this conclusion, some heroic assumptions need to be made. As such the method as developed here only reflects a first approximation. It needs to be used with care and is not intended to replace good comparative research.Antiepileptic drugs, Cost effectiveness, Epilepsy, Lamotrigine, Pharmacoeconomics, Topiramate

Enabling patient-reported outcome measures in clinical trials, exemplified by cardiovascular trials

Abstract Objectives There has been limited success in achieving integration of patient-reported outcomes (PROs) in clinical trials. We describe how stakeholders envision a solution to this challenge. Methods Stakeholders from academia, industry, non-profits, insurers, clinicians, and the Food and Drug Administration convened at a Think Tank meeting funded by the Duke Clinical Research Institute to discuss the challenges of incorporating PROs into clinical trials and how to address those challenges. Using examples from cardiovascular trials, this article describes a potential path forward with a focus on applications in the United States. Results Think Tank members identified one key challenge: a common understanding of the level of evidence that is necessary to support patient-reported outcome measures (PROMs) in trials. Think Tank participants discussed the possibility of creating general evidentiary standards depending upon contextual factors, but such guidelines could not be feasibly developed because many contextual factors are at play. The attendees posited that a more informative approach to PROM evidentiary standards would be to develop validity arguments akin to courtroom briefs, which would emphasize a compelling rationale (interpretation/use argument) to support a PROM within a specific context. Participants envisioned a future in which validity arguments would be publicly available via a repository, which would be indexed by contextual factors, clinical populations, and types of claims. Conclusions A publicly available repository would help stakeholders better understand what a community believes constitutes compelling support for a specific PROM in a trial. Our proposed strategy is expected to facilitate the incorporation of PROMs into cardiovascular clinical trials and trials in general

Les sous-communs: planification fugitive et étude noire

The Undercommons: Fugitive Planning & Black Study, Minor Compositions, 2013).Les sous-communs, planification fugitive et étude noire est une série d'essais publiée en 2013 par deux amis, Stefano Harney et Fred Moten. Au fil de ces textes, les auteurs proposent une critique du capitalisme racial et de ses outils (gouvernance, crédit, université) ainsi que des modes d'expérimentation sociale en forme de résistance au colonial. La recherche passe par l'étude et se déroule bien au-delà de l'université, au travail, lors d'une pause cigarette, en famille, autour d'un repas, à la lisière de la lutte et de la fuite, à l'intérieur d'un mouvement de tremblement des fondations impérialistes, d'un mouvement de refus des termes du combat tel qu'il est imposé par le système dominant, vers la construction d'un espace social et politique en perpétuel déplacement. Le lieu et l'être sous-communs relèvent de l'incertitude de la création collective, de l'habitation par l'échange, de l'improvisation comme critique.Les sous-communs s'écrit dans le sillage de la tradition radicale noire de manière à la fois théorique et poétique, auprés d'auteur*ices comme Cedric Robinson, Saidiya Hartman, Frantz Fanon et Édouard Glissant .La multitude profite de chaque temps calme, chaque crépuscule, chaque instant de préservation militante, pour planifier ensemble, lancer, composer (dans) son temps surréel.- Moten et Harney, p. 92.Stefano Harney est chercheur en sociologie et enseignant. Co-fondateur de la résidence de lecture Ground Provisions et du collectif d'enseignant*es School for Study, il est l'auteur de The Liberal Arts and Management Education (2020), Nationalism & Identity Culture (2006) et State Work: Public Administration and Mass Intellectuality (2002).Fred Moten est poète et professeur au département de Performance Studies de l'Université de New York, Tisch School of the Arts. Il est l'auteur de la trilogie consent not to be a single being, The Universal Machine (2018) ; Stolen Life (2018) et Black and Blur, (2017) ; The Service Porch (2016) ; B Jenkins (2010) ; In the Break: The Aesthetics of the Black Radical Tradition (2003)

Reduced Cancer Incidence in Huntington's Disease: Analysis in the Registry Study

Background: People with Huntington's disease (HD) have been observed to have lower rates of cancers. Objective: To investigate the relationship between age of onset of HD, CAG repeat length, and cancer diagnosis. Methods: Data were obtained from the European Huntington's disease network REGISTRY study for 6540 subjects. Population cancer incidence was ascertained from the GLOBOCAN database to obtain standardised incidence ratios of cancers in the REGISTRY subjects. Results: 173/6528 HD REGISTRY subjects had had a cancer diagnosis. The age-standardised incidence rate of all cancers in the REGISTRY HD population was 0.26 (CI 0.22-0.30). Individual cancers showed a lower age-standardised incidence rate compared with the control population with prostate and colorectal cancers showing the lowest rates. There was no effect of CAG length on the likelihood of cancer, but a cancer diagnosis within the last year was associated with a greatly increased rate of HD onset (Hazard Ratio 18.94, p < 0.001). Conclusions: Cancer is less common than expected in the HD population, confirming previous reports. However, this does not appear to be related to CAG length in HTT. A recent diagnosis of cancer increases the risk of HD onset at any age, likely due to increased investigation following a cancer diagnosis