A survey of new oncology drug approvals in the USA from 2010 to 2015: a focus on optimal dose and related postmarketing activities.
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ABSTRACT:
SUBMITTER: Lu D
PROVIDER: S-EPMC4767861 | biostudies-other | 2016 Mar
REPOSITORIES: biostudies-other
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Project description:The US Food and Drug Administration (FDA) issued a guidance document in 2010 on pharmacokinetic (PK) studies in renal impairment (RI) on the basis of observations that substances such as uremic toxins might result in altered drug metabolism and excretion. No specific recommendations for oncology drugs were included. We surveyed the publicly available FDA review documents of 29 small molecule oncology drugs approved between 2010 and the first quarter of 2015. The objectives were as follows: (i) summarize the impact of RI on PK at the time of the initial new drug application; (ii) identify limitations of the guidance; and (iii) outline an integrated approach to study the impact of RI on these drugs. Our survey indicates that the current FDA guidance does not appear to provide clear strategic or decision pathways for RI studies in terms of small molecule oncology drugs. The FDA review documents indicate an individualized approach to the review because of the complex pharmacologic nature of these drugs and patient populations. Overall, the strategy for carrying out a RI study during clinical development or as a postmarketing study requires integration with the totality of data, including mass balance, absolute bioavailability, drug-drug interaction, hepatic dysfunction, population PK, exposure-response analysis, the therapeutic window for best guidance, and determination of the optimal doses for special oncology populations.
| S-EPMC5515635 | biostudies-literature
Project description:BackgroundProtecting the health of refugees and other migrant populations in the United States is key to ensuring successful resettlement. Therefore, to identify and address health concerns early, the US Centers for Disease Control and Prevention (CDC) recommends a domestic medical examination (screening for infectious and noninfectious diseases/conditions) shortly after arrival in the US. However, because refugee/migrant populations often have differing health patterns from one another and the US population, the collection and analysis of health information is key to developing population-specific clinical guidelines to guide the care of resettled individuals. Yet little is known regarding the health status of Cubans resettling in the US. Among the tens of thousands of Cuban migrants who have resettled in the US, some applied as refugees in Cuba, some applied for parole (a term used to indicate temporary US admission status for urgent humanitarian reasons or reasons of public benefit under US immigration law) in Cuba, and others applied for parole status after crossing the border. These groups were eligible for US government benefits to help them resettle, including a domestic medical examination. We reviewed health differences found in these examinations of those who were determined to be refugees or parolees in Cuba and those who were given parole status after arrival.Methods and findingsWe conducted a retrospective cross-sectional analysis of the Texas Department of State Health Services database. Cubans who arrived from 2010 to 2015 and received a domestic medical examination in Texas were included. Those granted refugee/parolee status in Cuba were listed in federal databases for US-bound refugees/parolees; those who were paroled after arrival were not listed. Overall, 2,189 (20%) obtained either refugee or parolee status in Cuba, and 8,709 (80%) received parolee status after arrival. Approximately 62% of those who received parolee status after arrival at the border were male, compared with 49% of those who obtained prior refugee/parolee status in Cuba. Approximately one-half (45%) of those paroled after arrival were 19-34 years old (versus 26% among those who obtained refugee/parolee status in Cuba). Separate models were created for each screening indicator as the outcome, with entry route as the main exposure variable. Crude and adjusted prevalence ratios were estimated using PROC GENMOD procedures in SAS 9.4. Individuals paroled after arrival were less likely to screen positive for parasitic infections (9.6% versus 12.2%; adjusted prevalence ratio: 0.79, 0.71-0.88) and elevated blood lead levels (children ≤16 years old, 5.2% versus 12.3%; adjusted prevalence ratio: 0.42, 0.28-0.63). Limitations include potential disease misclassification, missing clinical information, and cross-sectional nature.ConclusionsWithin-country variations in health status are often not examined in refugee populations, yet they are critical to understand granular health trends. Results suggests that the health profiles of Cuban Americans in Texas differed by entry route. This information could assist in developing targeted screenings and health interventions.
| S-EPMC7428019 | biostudies-literature
Project description:The rates of pulmonary colonization and disease due to nontuberculous mycobacteria (NTM) appear to be increasing globally, but diversity of species recovered as well as clinical relevance of NTM isolates differ considerably by geographic region. The first nationwide study of isolation frequency and clinical significance of NTM in Serbia included all patients with respiratory specimens yielding a positive NTM culture over the six-year period, 2010-2015. We analyzed trends in annual NTM isolation and NTM pulmonary disease (PD) incidence rates, with NTM PD cases defined in accordance with microbiological criteria established by the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA). 777 pulmonary NTM isolates were collected from 565 patients, of whom 126 (22.3%) met the ATS/IDSA criteria. The annual NTM isolation and NTM PD incidence rates per 100,000 changed over 2010-2015 from 0.9 to 1.6 (p = 0.1746) and from 0.18 to 0.48 (p = f0.0040), respectively. Both isolation and disease rates increased considerably with age, while higher NTM PD rates were also associated with residence in urbanized areas. Diversity of NTM species isolated was shown to be region-specific, with M. xenopi as the most prevalent species (17.3%), and increasing isolation rates of rapid growing mycobacteria (RGM) (p = 0.0072). M. xenopi was also the most common cause of NTM PD (28.6%), followed by RGM (27.8%). With 73% clinically relevant isolates, M. abscessus was identified as the most clinically relevant NTM species. While NTM PD obviously remains a rare disease in Serbia, the overall results justify recognition of NTM as pathogens of rising importance, and require further characterization of their epidemiology in the country.
| S-EPMC6248987 | biostudies-literature
Project description:OBJECTIVES:To examine (1) the association between household socioeconomic status (SES) and whether a household spends money on cigarettes and (2) socioeconomic variations in proportion of total household expenditure spent on cigarettes among smoking households. METHODS:We pooled data from six consecutive years, 2010-2015, of the Consumer Expenditure Interview Survey. The interviews involved a structured questionnaire about household income, demographics and expenditures including expenditure on cigarettes. Households that reported cigarette expenditure in the previous 3?months were distinguished as smoking households. SES indicators were household poverty status, education and occupation of the head of household. Logistic regression was used to assess the association of household smoking status with SES. Fractional logistic regression was used to assess the association of cigarette expenditure as a proportion of total household expenditure with SES. The analysis sample size was 39?218. RESULTS:The probability of spending money on cigarettes was higher among lower SES households. Households in poverty compared with those above 300% of poverty threshold had 1.86 (95% CI 1.61 to 2.16), households headed by a person with less than high school education compared with those headed by a person with at least a bachelor's degree had 3.37 (95% CI 2.92 to 3.89) and households headed by a blue-collar work compared with those headed by a person in a managerial occupation had 1.45 (95% CI 1.26 to 1.66) higher odds of spending money on cigarettes. Similarly, the proportion of total household expenditure spent on cigarettes was higher among lower SES smoking households. CONCLUSION:Lower SES households are more likely to spend money on cigarettes and spend a larger proportion of their total expenditure on cigarettes. We recommend strategies effective in reducing smoking among low SES smokers.
| S-EPMC6009464 | biostudies-literature
Project description:Purpose/objectivesMonte Carlo (MC) dose calculation has appeared in primary commercial treatment-planning systems and various in-house platforms. Dual-energy computed tomography (DECT) and metal artifact reduction (MAR) techniques complement MC capabilities. However, no publications have yet reported how proton therapy centers implement these new technologies, and a national survey is required to determine the feasibility of including MC and companion techniques in cooperative group clinical trials.Materials/methodsA 9-question survey was designed to query key clinical parameters: scope of MC utilization, validation methods for heterogeneities, clinical site-specific imaging guidance, proton range uncertainties, and how implants are handled. A national survey was distributed to all 29 operational US proton therapy centers on 13 May 2019.ResultsWe received responses from 25 centers (86% participation). Commercial MC was most commonly used for primary plan optimization (16 centers) or primary dose evaluation (18 centers), while in-house MC was used more frequently for secondary dose evaluation (7 centers). Based on the survey, MC was used infrequently for gastrointestinal, genitourinary, gynecology and extremity compared with other more heterogeneous disease sites (P < .007). Although many centers had published DECT research, only 3/25 centers had implemented DECT clinically, either in the treatment-planning system or to override implant materials. Most centers (64%) treated patients with metal implants on a case-by-case basis, with a variety of methods reported. Twenty-four centers (96%) used MAR images and overrode the surrounding tissue artifacts; however, there was no consensus on how to determine metal dimension, materials density, or stopping powers.ConclusionThe use of MC for primary dose calculation and optimization was prevalent and, therefore, likely feasible for clinical trials. There was consensus to use MAR and override tissues surrounding metals but no consensus about how to use DECT and MAR for human tissues and implants. Development and standardization of these advanced technologies are strongly encouraged for vendors and clinical physicists.
| S-EPMC8489489 | biostudies-literature
Project description:In modern societies, cultural change seems ceaseless. The flux of fashion is especially obvious for popular music. While much has been written about the origin and evolution of pop, most claims about its history are anecdotal rather than scientific in nature. To rectify this, we investigate the US Billboard Hot 100 between 1960 and 2010. Using music information retrieval and text-mining tools, we analyse the musical properties of approximately 17 000 recordings that appeared in the charts and demonstrate quantitative trends in their harmonic and timbral properties. We then use these properties to produce an audio-based classification of musical styles and study the evolution of musical diversity and disparity, testing, and rejecting, several classical theories of cultural change. Finally, we investigate whether pop musical evolution has been gradual or punctuated. We show that, although pop music has evolved continuously, it did so with particular rapidity during three stylistic 'revolutions' around 1964, 1983 and 1991. We conclude by discussing how our study points the way to a quantitative science of cultural change.
| S-EPMC4453253 | biostudies-literature
Project description:BackgroundContinuous metabolic syndrome (MS) severity scores that can track metabolic risk in individuals over time have been developed for Western populations. The present study aimed to develop gender- and age-specific equations for MS severity scores in Korean adults.MethodsUsing data from the Korea National Health and Nutrition Examination Surveys (KNHANES) IV (2010-2012) and VI (2013-2015), we performed a confirmatory factor analysis of single MS factor that allowed for differential loadings across groups to generate gender- and age-specific, continuous MS severity scores. Then, we validated this equation in a different dataset of Korean adults.ResultsIn confirmatory analysis, waist circumference had the highest factor loading, indicating that waist circumference had the strongest correlation with MS among Korean adults. Lower factor loadings (< 0.4) among Korean adults aged 40-59 years were noted for systolic blood pressure and fasting glucose. MS severity score values were significantly correlated with metabolic parameters, including high-sensitivity C-reactive-protein, glycated hemoglobin, and homeostasis model assessment of insulin resistance. Furthermore, MS severity scores well predicted traditional MS according to receiver operating characteristic analysis in a validation dataset (KNHANES VII). In a longitudinal cohort dataset, participants diagnosed with Adult Treatment Program III (ATP-III) MS after an initial assessment had progressively higher baseline MS severity scores in relationship to their time until ATP-III MS diagnosis.ConclusionThe new MS severity score equations for Korean adults proposed in this study provide a clinically-accessible continuous measure of MS for potential use in identifying adults at higher risk for MS-related diseases and following changes within individuals over time.
| S-EPMC6374550 | biostudies-literature
Project description:ObjectiveThis study presents national surveys of patient exposure from nuclear medicine (NM) diagnostic procedures in 2010 and 2015 in the Republic of Croatia.MethodsThe survey was performed according to the European Commission Dose DataMed (DDM) project methodology. 28 most frequent NM diagnostic procedures were identified. Data about frequencies of procedures and average administered activities of radioisotopes used in those procedures were collected. Average administered activities were converted to effective doses according to the dose conversion coefficients. Then the collective effective dose to the population and an effective dose per capita were calculated based on the number of the most frequent NM diagnostic procedures and the average effective dose per procedure.ResultsIn 2010, 41200 NM diagnostic procedures led to 146.7 manSv collective effective dose to the population and in 2015, 42000 NM diagnostic procedures led to 146.8 manSv collective effective dose to the population. The frequencies of NM diagnostic procedures were 9.7 and 9.8 annually per 1000 population with 34.1 μSv and 34.2 μSv effective dose per capita for 2010 and 2015, respectively. The main contributors to the annual collective dose from NM in Croatia are examinations of the bone, heart, thyroid and PET/CT tumour diagnostic. Average administered activities have not changed considerably from 2010 to 2015. Nevertheless, within the frequency of some of the procedures, significant changes were found in five-year period.ConclusionsFrequencies, average administered activities and collective effective dose to the population from NM diagnostic procedures in Croatia are comparable to the values reported by other European surveys. Changes were found between 2010 and 2015 and we intend to perform this study periodically to identify possible trends, but also to raise awareness about the potential dose optimization.
| S-EPMC5491126 | biostudies-literature
Project description: Not available
| S-EPMC3310564 | biostudies-literature
Project description:The Centers for Disease Control and Prevention (CDC), in collaboration with the West Virginia Bureau of Public Health (BPH), initiated an investigation to characterize private well water quality in West Virginia. The objective was to better characterize private well water across various aquifer geologies by testing household drinking water samples and comparing them to EPA's National Primary Drinking Water Standards. The BPH selected ten counties representing three regions to capture geologically diverse areas that represent varying aquifer geology. We collected well-water samples from participating households and analyzed all water samples for 20 constituents currently monitored in public drinking-water systems. We calculated geometric means for each constituent and compared metal concentrations to EPA maximum and secondary contaminant levels by the geologic age of the rock surrounding the aquifer where the sample was obtained. All participating households (n=139) provided a water sample. We detected arsenic at levels higher than the EPA maximum contaminant level in 10 (7.2%) samples. We detected elevated radon-222 in 48 (34.5%) samples. Geologic age of the region was indicative of whether arsenic and radon-222 were present at levels that exceeded current EPA drinking water standards. We found arsenic and radon concentrations were higher in Permian aquifers compared to those of other geologic ages. Homeowners with private wells in areas with Permian aged aquifers could benefit from targeted public health messaging about potentially harmful constituent concentrations in the well water. This may help ensure proper testing and maintenance of private wells and reduce exposure to these constituents.
| S-EPMC5590756 | biostudies-literature