118 research outputs found
A four-step strategy for handling missing outcome data in randomised trials affected by a pandemic.
BACKGROUND: The coronavirus pandemic (Covid-19) presents a variety of challenges for ongoing clinical trials, including an inevitably higher rate of missing outcome data, with new and non-standard reasons for missingness. International drug trial guidelines recommend trialists review plans for handling missing data in the conduct and statistical analysis, but clear recommendations are lacking. METHODS: We present a four-step strategy for handling missing outcome data in the analysis of randomised trials that are ongoing during a pandemic. We consider handling missing data arising due to (i) participant infection, (ii) treatment disruptions and (iii) loss to follow-up. We consider both settings where treatment effects for a 'pandemic-free world' and 'world including a pandemic' are of interest. RESULTS: In any trial, investigators should; (1) Clarify the treatment estimand of interest with respect to the occurrence of the pandemic; (2) Establish what data are missing for the chosen estimand; (3) Perform primary analysis under the most plausible missing data assumptions followed by; (4) Sensitivity analysis under alternative plausible assumptions. To obtain an estimate of the treatment effect in a 'pandemic-free world', participant data that are clinically affected by the pandemic (directly due to infection or indirectly via treatment disruptions) are not relevant and can be set to missing. For primary analysis, a missing-at-random assumption that conditions on all observed data that are expected to be associated with both the outcome and missingness may be most plausible. For the treatment effect in the 'world including a pandemic', all participant data is relevant and should be included in the analysis. For primary analysis, a missing-at-random assumption - potentially incorporating a pandemic time-period indicator and participant infection status - or a missing-not-at-random assumption with a poorer response may be most relevant, depending on the setting. In all scenarios, sensitivity analysis under credible missing-not-at-random assumptions should be used to evaluate the robustness of results. We highlight controlled multiple imputation as an accessible tool for conducting sensitivity analyses. CONCLUSIONS: Missing data problems will be exacerbated for trials active during the Covid-19 pandemic. This four-step strategy will facilitate clear thinking about the appropriate analysis for relevant questions of interest
Randomised controlled trial of adjunctive triamcinolone acetonide in eyes undergoing vitreoretinal surgery following open globe trauma: The ASCOT study
Adverse event reporting in randomised trials of neuropathic pain: challenges for clinical usefulness of safety data
Preconceptional, Gestational, and Lactational Exposure to an Unconventional Oil and Gas Chemical Mixture Alters Energy Expenditure in Adult Female Mice
Previous studies conducted in our laboratory have found altered adult health outcomes in animals with prenatal exposure to environmentally relevant levels of unconventional oil and gas (UOG) chemicals with endocrine-disrupting activity. This study aimed to examine potential metabolic health outcomes following a preconception, prenatal and postnatal exposure to a mixture of 23 UOG chemicals. Prior to mating and from gestation day 1 to postnatal day 21, C57BL/6J mice were developmentally exposed to a laboratory-created mixture of 23 UOG chemicals in maternal drinking water. Body composition, spontaneous activity, energy expenditure, and glucose tolerance were evaluated in 7-month-old female offspring. Neither body weight nor body composition differed in 7-month female mice. However, females exposed to 1.5 and 150 μg/kg/day UOG mix had lower total and resting energy expenditure within the dark cycle. In the light cycle, the 1,500 μg//kg/day group had lower total energy expenditure and the 1.5 μg/kg/day group had lower resting energy expenditure. Females exposed to the 150 μg/kg/day group had lower spontaneous activity in the dark cycle, and females exposed to the 1,500 μg/kg/day group had lower activity in the light cycle. This study reports for the first time that developmental exposure to a mixture of 23 UOG chemicals alters energy expenditure and spontaneous activity in adult female mice
A phase III, multi-centre, double-masked randomised controlled trial of adjunctive intraocular and peri-ocular steroid (triamcinolone acetonide) versus standard treatment in eyes undergoing vitreoretinal surgery for open globe trauma (ASCOT): statistical analysis plan
A cluster randomised feasibility study of an adolescent incentive intervention to increase uptake of HPV vaccination.
BACKGROUND: Uptake of human papillomavirus (HPV) vaccination is suboptimal among some groups. We aimed to determine the feasibility of undertaking a cluster randomised controlled trial (RCT) of incentives to improve HPV vaccination uptake by increasing consent form return. METHODS: An equal-allocation, two-arm cluster RCT design was used. We invited 60 London schools to participate. Those agreeing were randomised to either a standard invitation or incentive intervention arm, in which Year 8 girls had the chance to win a £50 shopping voucher if they returned a vaccination consent form, regardless of whether consent was provided. We collected data on school and parent participation rates and questionnaire response rates. Analyses were descriptive. RESULTS: Six schools completed the trial and only 3% of parents opted out. The response rate was 70% for the girls' questionnaire and 17% for the parents'. In the intervention arm, 87% of girls returned a consent form compared with 67% in the standard invitation arm. The proportion of girls whose parents gave consent for vaccination was higher in the intervention arm (76%) than the standard invitation arm (61%). CONCLUSIONS: An RCT of an incentive intervention is feasible. The intervention may improve vaccination uptake but a fully powered RCT is needed.British Journal of Cancer advance online publication: 22 August 2017; doi:10.1038/bjc.2017.284 www.bjcancer.com
The Rise of Adaptive Platform Trials in Critical Care
As durable learning research systems, adaptive platform trials represent a transformative new approach to accelerating clinical evaluation and discovery in critical care. This Perspective provides a brief introduction to the concept of adaptive platform trials, describes several established and emerging platforms in critical care, and surveys some opportunities and challenges for their implementation and impact.<br/
The role of anti-IgE (omalizumab/Xolair) in the management of severe recalcitrant paediatric atopic eczema (ADAPT): statistical analysis plan
Tolerance of allogromiid Foraminifera to severely elevated carbon dioxide concentrations : implications to future ecosystem functioning and paleoceanographic interpretations
Author Posting. © Elsevier B.V., 2009. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Global and Planetary Change 65 (2009): 107-114, doi:10.1016/j.gloplacha.2008.10.013.Increases in the partial pressure of carbon dioxide (pCO2) in the atmosphere will
significantly affect a wide variety of terrestrial fauna and flora. Because of tight atmospheric-oceanic
coupling, shallow-water marine species are also expected to be affected by increases in
atmospheric carbon dioxide concentrations. One proposed way to slow increases in atmospheric
pCO2 is to sequester CO2 in the deep sea. Thus, over the next few centuries marine species will
be exposed to changing seawater chemistry caused by ocean-atmospheric exchange and/or deep-ocean
sequestration. This initial case study on one allogromiid foraminiferal species
(Allogromia laticollaris) was conducted to begin to ascertain the effect of elevated pCO2 on
benthic Foraminifera, which are a major meiofaunal constituent of shallow- and deep-water
marine communities. Cultures of this thecate foraminiferan protist were used for 10-14-day
experiments. Experimental treatments were executed in an incubator that controlled CO2 (15
000; 30 000; 60 000; 90 000; 200 000 ppm), temperature and humidity; atmospheric controls
(i.e., ~375 ppm CO2) were executed simultaneously. Although the experimental elevated pCO2
values are far above foreseeable surface water pCO2, they were selected to represent the
spectrum of conditions expected for the benthos if deep-sea CO2 sequestration becomes a reality.
Survival was assessed in two independent ways: pseudopodial presence/absence and
measurement of adenosine triphosphate (ATP), which is an indicator of cellular energy.
Substantial proportions of A. laticollaris populations survived 200 000 ppm CO2 although the
mean of the median [ATP] of survivors was statistically lower for this treatment than for that of
atmospheric control specimens. After individuals that had been incubated in 200 000 ppm CO2
for 12 days were transferred to atmospheric conditions for ~24 hours, the [ATP] of live
specimens (survivors) approximated those of the comparable atmospheric control treatment.
Incubation in 200 000 ppm CO2 also resulted in reproduction by some individuals. Results
suggest that certain Foraminifera are able to tolerate deep-sea CO2 sequestration and perhaps
thrive as a result of elevated pCO2 that is predicted for the next few centuries, in a high-pCO2
world. Thus, allogromiid foraminiferal “blooms” may result from climate change. Furthermore,
because allogromiids consume a variety of prey, it is likely that they will be major players in
ecosystem dynamics of future coastal sedimentary environments.This work was funded by US Department of Energy grant # DE-FG02-03ER63696 (to
J. Kennett and J. Bernhard), NSF OCE-0725966, and the WHOI Summer Student Fellow
Program, which is funded by NSF Research Experience for Undergraduates Program grant
#OCE-0139423
A Qualitative View of Drug Use Behaviors of Mexican Male Injection Drug Users Deported from the United States
Deportees are a hidden yet highly vulnerable and numerous population. Significantly, little data exists about the substance use and deportation experiences of Mexicans deported from the United States. This pilot qualitative study describes illicit drug use behaviors among 24 Mexico-born male injection drug users (IDUs), ≥18 years old, residing in Tijuana, Mexico who self-identified as deportees from the United States. In-person interviews were conducted in Tijuana, Mexico in 2008. Content analysis of interview transcripts identified major themes in participants’ experiences. Few participants had personal or family exposures to illicit drugs prior to their first U.S. migration. Participants reported numerous deportations. Social (i.e., friends/family, post-migration stressors) and environmental factors (e.g., drug availability) were perceived to contribute to substance use initiation in the U.S. Drugs consumed in the United States included marijuana, heroin, cocaine, methamphetamine, and crack. More than half of men were IDUs prior to deportation. Addiction and justice system experiences reportedly contributed to deportation. After deportation, several men injected new drugs, primarily heroin or methamphetamine, or a combination of both drugs. Many men perceived an increase in their substance use after deportation and reported shame and loss of familial social and economic support. Early intervention is needed to stem illicit drug use in Mexican migrant youths. Binational cooperation around migrant health issues is warranted. Migrant-oriented programs may expand components that address mental health and drug use behaviors in an effort to reduce transmission of blood-borne infections. Special considerations are merited for substance users in correctional systems in the United States and Mexico, as well as substance users in United States immigration detention centers. The health status and health behaviors of deportees are likely to impact receiving Mexican communities. Programs that address health, social, and economic issues may aid deportees in resettling in Mexico
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