Generic drug competition: The pharmaceutical industry “gaming” controversy

Among American adults 20 years and older, 59 percent take at least one prescription drug on a regular basis. Unlike most branded drugs, which are generally drugs that have a trade name and are protected by a patent, off‐patent generic drugs make up approximately 90 percent of prescriptions annually filled in the United States; yet in 2017, generic drugs made up only 23 percent of total drug costs in the U.S. The U.S. Food and Drug Administration has taken the lead in encouraging increased competition in the nation’s prescription drug marketplace, most recently with its release of the agency’s Drug Competition Action Plan, but also with its regulatory guidance and enforcement efforts to eliminate “gaming” of the regulatory process by both branded and generic pharmaceutical manufacturers. Such “gaming” activities include “pay‐for‐delay” agreements involving financial compensation between branded and generic pharmaceutical manufacturers to forestall the emergence into the market of generic pharmaceuticals to compete against a formerly patent‐protected branded drug. A combination of new enabling legislation, federal judicial guidance, and agency regulatory activities show promise in encouraging increased competition in the prescription drug marketplace, with the American consumer the ultimate beneficiary of lower health care costs and improved overall personal health.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152498/1/basr12186_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152498/2/basr12186.pd

Colorants in Cheese Manufacture: Production, Chemistry, Interactions, and Regulation

Colored Cheddar cheeses are prepared by adding an aqueous annatto extract (norbixin) to cheese milk; however, a considerable proportion (∼20%) of such colorant is transferred to whey, which can limit the end use applications of whey products. Different geographical regions have adopted various strategies for handling whey derived from colored cheeses production. For example, in the United States, whey products are treated with oxidizing agents such as hydrogen peroxide and benzoyl peroxide to obtain white and colorless spray‐dried products; however, chemical bleaching of whey is prohibited in Europe and China. Fundamental studies have focused on understanding the interactions between colorants molecules and various components of cheese. In addition, the selective delivery of colorants to the cheese curd through approaches such as encapsulated norbixin and microcapsules of bixin or use of alternative colorants, including fat‐soluble/emulsified versions of annatto or beta‐carotene, has been studied. This review provides a critical analysis of pertinent scientific and patent literature pertaining to colorant delivery in cheese and various types of colorant products on the market for cheese manufacture, and also considers interactions between colorant molecules and cheese components; various strategies for elimination of color transfer to whey during cheese manufacture are also discussed

Emergency Research: Using Exception from Informed Consent, Evaluation of Community Consultations

Background In 1996, the U.S. Food and Drug Administration approved regulations authorizing an exception from informed consent (EFIC) for research conducted in emergency settings when obtaining prospective informed consent is not possible due to the potential subject's critical illness or injury. The regulations require that investigators conduct community consultation (CC) efforts before initiating a study and require that institutional review boards review the results of CC prior to approving a study. However, little is known about how communities view EFIC research or the CC process. Objectives The objective was to assess the views of CC meeting attendees regarding the CC process, their understanding and views of EFIC research relating to the specific research trial under discussion, and their level of trust in physician‐investigators. Methods Following CC meetings at two study sites (San Francisco and Atlanta) for the Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART), an active comparison, randomized trial of prehospital treatment for status epilepticus, the authors administered a pair of surveys to participants. One survey focused on CC experiences (CC survey) and trust in physician‐investigators; the second assessed participants' understanding of EFIC and the RAMPART clinical trial design (EFIC survey). Results A total of 317 individuals participated in one of the two most popular types of CC meetings (group meetings and focus group sessions) at both sites. A total of 189 participants (59%) completed the CC survey and trust questions, and 297 (92%) completed the EFIC survey. Of those who completed the CC survey, 173 of 189 (92%) were very satisfied with the meeting, and 174 of 189 (92%) felt that they learned a lot about research at the meeting. A total of 169 of 189 participants (88%) felt that researchers heard the community's concerns, while only 106 of 189 (56%) said researchers would be willing to make changes to the study based on their concerns. Of those who completed the EFIC survey, 261 of 297 (88%) supported the study, 207 of 297 (70%) said they would agree to participate in the study, and 203 of 297 (68%) reported that they would agree to consent a loved one into the study. On a recently validated scale measuring trust in physician‐investigators, participants at both sites seemed to have higher levels of trust in physician‐investigators than the validation study population. Conclusions Overall, members of these two communities expressed satisfaction with the CC session and had relatively high levels of support for the study and trust in physician‐investigators. Resumen La Excepción del Consentimiento Informado en la Investigación en Medicina de Urgencias y Emergencias ‐ Evaluación de las Consultas a la Comunidad Introducción En 1996, la United States Food and Drug Administration aprobó las regulaciones que autorizaban la excepción del consentimiento informado (EDCI) para la investigación llevada a cabo en el ámbito de la medicina de urgencias y emergencias cuando la obtención del consentimiento informado de forma prospectiva no era posible debido a enfermedad o lesión potencialmente crítica del sujeto. Las regulaciones requieren que los investigadores hagan el esfuerzo de llevar a cabo una consulta comunitaria (CC) antes del inicio de un estudio, y requieren que el comité de revisores de la institución revise los resultados de la CC previamente a aprobación. Sin embargo, existe escasa información del punto de vista de las comunidades sobre la investigación con EDCI o el proceso de CC. Objetivos Valorar los puntos de vista de los asistentes a una reunión de CC respecto al proceso de CC, su grado de comprensión, su parecer respecto a la investigación con EDCI en relación al ensayo clínico en discusión y su nivel de confianza en los médicos investigadores. Método Tras las reuniones de CC en dos lugares (San Francisco y Atlanta) para evaluar el estudio Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART), un ensayo clínico con comparación activa y asignación aleatorizada del tratamiento prehospitalario para el estatus epiléptico, los autores administraron un par de encuestas a los participantes de la CC. Una encuesta se enfocó a las experiencias de CC (encuesta CC) y la confianza en los médicos investigadores; la segunda valoró el grado de comprensión de los participantes acerca de la EDCI y el diseño del ensayo clínico RAMPART (encuesta EDCI). Resultados Un total de 317 sujetos participaron en una de las dos sesiones de CC más populares (reuniones de grupo y sesiones de grupo dirigidas) en ambos lugares. Ciento ochenta y nueve participantes (59%) completaron la encuesta CC y las preguntas sobre el grado de confianza, y 297 (92%) completaron la encuesta EDCI. De aquéllos que completaron la encuesta CC, 173 de 189 (92%) estaban muy satisfechos con la reunión, y 174 de 189 (92%) expresaron que habían aprendido mucho sobre la investigación en la reunión. Ciento sesenta y seis de 189 participantes (88%) sintieron que los investigadores escucharon las inquietudes de la comunidad, mientras que sólo 106 de 189 (56%) afirmaron que los investigadores desearían realizar cambios en el estudio basándose en sus inquietudes. De aquéllos que completaron la encuesta EDCI, 261 de 297 (88%) apoyaron el estudio, 207 de 297(70%) dijeron que estarían de acuerdo en participar en el estudio, y 203 de 297 (68%) expresaron que estarían de acuerdo en dar el consentimiento de un ser querido para el estudio. Según una escala para medir la confianza en los médicos investigadores validada recientemente, los participantes de ambos lugares parecían tener mayores niveles de confianza en los médicos investigadores que la población de validación del estudio. Conclusiones En definitiva, los miembros de estas dos comunidades expresaron satisfacción con la sesión de CC y tuvieron niveles relativamente altos de aprobación del estudio y de confianza en los médicos investigadores.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96243/1/acem12039-sup-0003-DataSupplementS3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/96243/2/acem12039-sup-0001-DataSupplementS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/96243/3/acem12039.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/96243/4/acem12039-sup-0002-DataSupplementS2.pd

The application of precision dosing in the use of sertraline throughout pregnancy for poor and ultra-rapid metaboliser CYP 2C19 subjects: a virtual clinical trial pharmacokinetics study:A virtual clinical trial pharmacokinetics study

Sertraline is known to undergo changes in pharmacokinetics during pregnancy. CYP 2C19 has been implicated in the interindividual variation in clinical effect associated with sertraline activity. However, knowledge of suitable dose titrations during pregnancy and within CYP 2C19 phenotypes is lacking. A pharmacokinetic modeling virtual clinical trials approach was implemented to: (i) assess gestational changes in sertraline trough plasma concentrations for CYP 2C19 phenotypes, and (ii) identify appropriate dose titration strategies to stabilize sertraline levels within a defined therapeutic range throughout gestation. Sertraline trough plasma concentrations decreased throughout gestation, with maternal volume expansion and reduction in plasma albumin being identified as possible causative reasons. All CYP 2C19 phenotypes required a dose increase throughout gestation. For extensive metabolizer (EM) and ultrarapid metabolizer (UM) phenotypes, doses of 100–150 mg daily are required throughout gestation. For poor metabolizers (PM), 50 mg daily during trimester 1 followed by a dose of 100 mg daily in trimesters 2 and 3 are required

Genome-wide Association Study for Beta-glucan Concentration in Elite North American Oat

Genome-wide association studies (GWAS) can be a useful approach to detect quantitative trait loci (QTL) controlling complex traits in crop plants. Oat (Avena sativa L.) β-glucan is a soluble dietary fiber and has been shown to have positive health benefits. We report a GWAS involving 446 elite oat breeding lines from North America genotyped with 1005 diversity arrays technology (DArT) markers and with phenotypic data from both historical and balanced 2-yr data. Association analyses accounting for pair-wise relationships and population structure were conducted using single-marker tests and least absolute shrinkage and selection operator (LASSO). Single-marker tests yielded six and 15 significant markers for the historical and balanced data sets, respectively. The LASSO method selected 24 and 37 markers as the most important in explaining β-glucan concentration for the historical and balanced data sets, respectively. Comparisons of genetic location showed that 15 of the markers in our study were found on the same linkage groups as QTL identified in previous studies. Four of the markers colocalized to within 4 cM of three previously detected QTL, suggesting concordance between QTL detected in our study and previous studies. Two of the significant markers were also adjacent to a β-glucan candidate gene in the rice (Oryza sativa L.) genome. Our findings suggest that GWAS can be used for QTL detection for the purpose of gene discovery and for marker-assisted selection to improve β-glucan concentration in elite oat