Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Sample size estimation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 541 records · Page 30Linked to original sources
PubMed1998

Characterization of deleterious mutations in outcrossing populations.

Deng and Lynch recently proposed estimating the rate and effects of deleterious genomic mutations from changes in the mean and genetic variance of fitness upon selfing/outcrossing in outcrossing/highly selfing populations. The utility of our original estimation approach is limited in outcrossing populations, since selfing may not always be feasible. Here we extend the approach to any form of inbreeding in outcrossing populations. By simulations, the statistical properties of the estimation under a common form of inbreeding (sib mating) are investigated under a range of biologically plausible situations. The efficiencies of different degrees of inbreeding and two different experimental designs of estimation are also investigated. We found that estimation using the total genetic variation in the inbred generation is generally more efficient than employing the genetic variation among the mean of inbred families, and that higher degree of inbreeding employed in experiments yields higher power for estimation. The simulation results of the magnitude and direction of estimation bias under variable or epistatic mutation effects may provide a basis for accurate inferences of deleterious mutations. Simulations accounting for environmental variance of fitness suggest that, under full-sib mating, our extension can achieve reasonably well an estimation with sample sizes of only approximately 2000-3000.

Analysis of Variance↗
PubMed2005

A profile of home care workers from the 2000 census: how it changes what we know.

PURPOSE: The goal of our study was to identify a representative sample of direct care aides to generate an accurate profile of the long-term-care workforce, with a special focus on home care workers. DESIGN AND METHODS: Data were taken from the 5% Public Use Microdata Sample (PUMS) of the 2000 Census. RESULTS: Variable coding in the 2000 Census data allowed for a more detailed identification of long-term-care workers than was available in previous studies. On the basis of this new sample, the estimated size of the home care workforce is much larger than that in previous estimates, and it is more heterogeneous. In addition, our analyses revealed more self-employed workers, higher salaries than previously reported, and greater ethnic diversity, with Hispanics or Latinos comprising a significant proportion of the home care workforce. IMPLICATIONS: Numerous state and federal programs are currently underway to increase the capacity of the long-term-care workforce. A more comprehensive understanding of the characteristics of the long-term-care workforce will facilitate more effective development of programs designed to enhance recruitment and retention of these workers to meet the increasing demands of future years.

Adult↗
PubMed1999

Method to detect genotype-environment interactions for quantitative trait loci in association studies.

Khoury et al. (Am J Hum Genet 1988;42:89-95 and Am J Epidemiol 1993;137:1241-50) presented an epidemiologic approach to examine genotype-environment interaction in situations where the disease is either present or absent. In this article, the author extends the approach of Khoury et al. to quantitative outcome variables. This extension is relevant for diseases that are extremes on a continuum or when continuous risk factors are studied. To account for a possible admixture of subgroups in the sample, tests for genotype-environment interaction are discussed for designs with parents as controls as well as without parents as controls. Assuming two environmental conditions, the author demonstrates how the power of these tests can be calculated and used to estimate the sample sizes needed to detect genotype-environment interaction in a variety of conditions. In addition, he analyzes simulated data to demonstrate the detection of different mechanisms of genotype-environment interaction and to study the effectiveness of this approach to identify the correct mechanism. Finally, extensions to multiple environmental conditions and designs with multiple subjects per family are discussed.

Analysis of Variance↗
PubMed1987

Review: clinical trials in peptic ulcer disease--problems of methodology and interpretation.

This review focuses on the methodology and interpretation of drug trials in peptic ulcer disease. The problems of planning and conduct that are discussed include the ethics of using placebo, eligibility criteria, estimations of sample size, stopping rules, randomization, blinding, and efficacy criteria, that is, ulcer healing and pain relief in the short term and prevention of relapse and complications in the long term. Statistical topics covered include confidence intervals, evaluation of survival type data, post-stratification, and sub-group analysis. The difference between clinical and statistical significance is discussed, major problems being overemphasis on P-value, type II errors, and post hoc power determinations. Explanatory and pragmatic questions are based on compliance-to-protocol and intention-to-treat cohorts, respectively, and involve problems of compliance testing, evaluation of withdrawals, and the use of fixed-dose regimens. The rather slow process for clinical trials to gain acceptance is described, and it is proposed to rely on disease-related and behavioural barriers, lack of knowledge of the inherent limitations of methodology, and overemphasis on the subject of peptic ulcer healing, in addition to some concern at the relevance of assessing long-term drug intervention by repeated endoscopies rather than by studying symptoms and the incidence of complications. We foresee an increased impact of clinical trials on ulcer research and therapeutic decision making, provided physicians are able to develop the proper methodology to answer the relevant questions.

Anti-Ulcer Agents↗
PubMed2004

On the evolution of statistical methods as applied to clinical trials.

This paper describes how statistical methods have evolved in parallel with activities associated with randomized control trials. In particular we emphasize the pivotal role of two papers published in British Journal of Cancer, and the paper describing the Cox proportional hazards model. In addition, the importance of early papers on estimating the sample size required for trials is highlighted. Later developments including the increasing roles for competing risks, multilevel modelling and Bayesian methodologies are described. The interplay between computer software and statistical methodological developments is stressed. Finally some future directions are indicated.

Humans↗
PubMed1993

Unbiased volume estimation with coaxial sections: an application to the human bladder.

A problem of current medical interest is how to estimate the volume of an object from coaxial sections. Such images can be produced in ultrasound scanning, when the planar scan sections all emanate from a common axis. Two unbiased volume estimators for this sampling regime, previously published without derivation, are derived and presented here in some detail. The estimators are based on an ancient theorem of Pappus of Alexandria (c. AD 320). One of the estimators was used to estimate the volume of urine in the bladder of six human volunteers. The case example was attractive because the corresponding volumes could be voided and directly measured after the scanning session, thus confirming the unbiasedness of the estimator used. Sample size guidelines are also given.

Adult↗
PubMed2005

Evolution of methodological standards in surgical trials.

BACKGROUND: The Consolidated Standards of Reporting Trials (CONSORT) Statement outlines acceptable ways of performing and reporting clinical trials. The objective of the present study was to identify evolving patterns in the methodological standards of surgical trials. METHODS: Compliance with 12 key standards from the CONSORT statement were evaluated in 490 trials published in either the ANZ Journal of Surgery or the British Journal of Surgery between January 1969 and December 2003. RESULTS: There has been an irregular but progressive improvement in the methodological standards of published trials. The criteria with the greatest improvement related to estimation of sample size, randomization, concealment of the allocated intervention, baseline comparisons, and the method of expressing outcomes. Compliance rates were <50% for three criteria during the last decade of the review, that is, concealment of the allocated intervention, blindness of assessment, and the method of expressing outcomes. CONCLUSION: The results of surgical trials need to be interpreted with care.

Australia↗
PubMed1996

The effects of whirlpools baths in labor: a randomized, controlled trial.

BACKGROUND: Showers and tubs in labor were not generally used in our center. When three whirlpool baths (Jacuzzis) were ordered as part of our renovations, a randomized, controlled trial was initiated to explore their effects on narcotic and epidural requirements. METHODS: This study employed an intent-to-treat design, and the sample size was estimated to account for the fact that some women would be unable to use the tub. The experimental group of 393 women was offered the tub during labor and the control group of 392 women received conventional care. RESULTS: No births occurred in the tub. The tub group required fewer pharmacologic agents than controls (66% vs 59%, p = 0.06), experienced fewer deliveries by forceps and vacuum (p = 0.019), and were more likely to have an intact perineum than the standard-care group (p = 0.019). Labor was longer for the tub group (p = 0.003), who coincidentally were more primiparous and in earlier labor on admission. No differences were noted in the low rates of maternal and newborn signs of infection in women with ruptured membranes. A subset of mothers expressed satisfaction with the tub experience and labor support. The cesarean rate among both groups was lower (8.9%) than our overall rate (16.6%) during the study period. CONCLUSIONS: Whirlpool baths in labor have positive effects on analgesia requirements, instrumentation rates, condition of the perineum, and personal satisfaction. Further study is being planned.

Delivery Rooms↗
PubMed1999

The influence of in vitro nitroimidazole resistance on the efficacy of nitroimidazole-containing anti-Helicobacter pylori regimens: a meta-analysis.

OBJECTIVE: The aim of this study was to determine the influence of nitroimidazole resistance (NIR) on the efficacy of treatment for Helicobacter pylori (H. pylori) infections by meta-analysis of the world literature. METHODS: A MEDLINE search, a manual search of all major gastroenterological journals from 1993 to 1997, and abstracts of gastroenterological and H. pylori meetings from 1993 to 1997 were performed. All treatment studies using a nitroimidazole and providing data about the medication used, dose frequency, total daily dose, duration of treatment, and eradication results in relation to NIR were included. Eradication had to be assessed by two biopsy-based tests or a urea breath test > or = 4 wk after treatment. Individual studies were pooled into groups according to the medication used and the duration of treatment. The pooled estimate of the odds ratio (OR) of NIR for treatment failure and its 95% confidence interval (95% CI) were calculated for each group using the logit method. To detect any possible bias, funnel plots (plots of effect estimates against sample size) were constructed. RESULTS: A total of 91 treatment arms, including a total of 4823 patients, were evaluated. The pooled ORs of NIR for treatment failure (95% CI) of proton pump inhibitors, bismuth, and quadruple regimens were 5.2 (3.8-7.1), 5.9 (4.1-8.3), and 7.0 (3.1-16.0), respectively. Eradication rates were 90% in susceptible strains but <75% in resistant strains. In susceptible strains, neither treatment duration nor the choice of the second antibiotic influenced efficacy. In resistant strains, tetracycline was more effective than amoxicillin (bismuth regimens), and the longer the duration of regimens (bismuth-amoxicillin regimens) the more effective they were. Only quadruple regimens given for > or = 1 wk were effective in resistant strains. CONCLUSIONS: NIR decreases treatment efficacy. Treatment duration and choice of other drugs influence the impact of NIR on treatment efficacy. If NIR is present, a nitroimidazole-containing regimen should be avoided or a quadruple regimen should be given for > 1 wk.

Drug Resistance, Microbial↗
PubMed2025

Harnessing Landscape Genomics to Evaluate Genomic Vulnerability and Future Climate Resilience in an East Asia Perennial.

In this era of rapid climate change, understanding the adaptive potential of organisms is imperative for buffering biodiversity loss. Genomic forecasting provides invaluable insights into population vulnerability and adaptive potential under diverse climatic conditions, thereby facilitating management interventions and bolstering shaping species-specific germplasm conservation strategies. We primarily employed landscape genomics approaches, leveraging single-nucleotide polymorphisms obtained through whole-genome resequencing of 201 individuals across 43 Rheum palmatum complex populations, to pinpoint adaptive variation and its significance in the context of future climates, delineate seed zones, and establish guidelines for ex situ germplasm conservation. The species complex exhibited strong signatures of local adaptation and differential genomic vulnerabilities across its distribution range, with eastern lineage populations facing significant maladaptation risks under future climate scenarios. Using diverse datasets of putatively adaptive loci and climate change scenarios, we delineated three distinct seed zones within the species' range, estimated varying sample sizes per zone to capture most adaptive diversity, and predicted shifts in seed zone centroids ranging from 48.3 to 359.3&#x2009;km from historical distributions to mitigate climate change impacts. Collectively, our findings underscore the importance of integrating genomic and environmental data to forecast the adaptive trajectory of an East Asian perennial under anticipated climate changes, guide seed zone delineation for germplasm conservation and enhance population resilience. These results provide a blueprint for designing targeted conservation strategies and restoration plans in other imperilled species.

Climate Change↗
PubMed2004

International carotid stenting study: protocol for a randomised clinical trial comparing carotid stenting with endarterectomy in symptomatic carotid artery stenosis.

BACKGROUND: Carotid stenting avoids general anaesthesia, cranial nerve injury and the discomforts of surgical treatment of carotid stenosis. A systematic review of the randomised trials showed no overall difference in the major risks of endovascular treatment for carotid stenosis compared with surgery, but the confidence intervals were wide and both methods carried a significant risk of stroke. The use of protection devices appears to improve the safety of endovascular treatment, but there are little randomised data available about long-term outcomes. We have therefore set up an international, multicentre, randomised, controlled, open, prospective clinical trial, namely the International Carotid Stenting Study (ICSS), also known as CAVATAS-2. The objectives of the ICSS are to compare the risks, benefits and cost-effectiveness of a treatment policy of referral for carotid stenting compared with referral for carotid endarterectomy. METHODS: Centres are required to have a team with audited expertise in carotid endarterectomy and stenting procedures, including at least one neurologist or stroke physician, a surgeon and an interventionalist. Attendance at a carotid stenting training course is required. Centres with more limited experience can join the trial as probationary centres, but stenting must then be proctored by an experienced interventionalist. Symptomatic patients are included over the age of 40 years with atherosclerotic carotid stenosis, suitable for both stenting and surgery, and are randomised in equal proportions between carotid endarterectomy and stenting. Stents and other devices are chosen for use at the discretion of the interventionalists but must be approved by the devices committee. The protocol recommends that a cerebral protection system should be used whenever the operator thinks one can be safely deployed. The combination of aspirin and clopidogrel is recommended to cover stenting procedures. Standard or eversion endarterectomy is allowed using local or general anaesthesia, shunts or patches. All patients will receive best medical care. Patients will be followed up by neurologists at 30 days after treatment, 6 months after randomisation and then annually up to 5 years after randomisation. The primary outcome measure is the difference in the long-term rate of fatal or disabling stroke in any territory between patients randomised to stenting or surgery. Secondary outcome measures include any stroke, myocardial infarction or death within 30 days of treatment, treatment- related cranial nerve palsy or haematoma. Restenosis (>70%) on ultrasound follow-up, economic measures and quality of life will also be analysed. The sample size is estimated at 1,500 patients, which will provide 95% confidence intervals of +/- 3.0 percentage points for the outcome measure of 30-day disabling stroke and death rate and +/- 3.3 percentage points for the outcome measure of death or stroke during follow-up. The trial office monitors outcome events at individual centres and a rate of events above a given threshold triggers a blinded assessment of the events, submitted to the chairman of the data-monitoring committee. CONCLUSIONS: The ICSS protocol incorporates a number of novel features to ensure patient safety, including the concept of probationary centres, proctoring of inexperienced investigators and monitoring of individual centre results on an ongoing basis. The protocol is also designed to mirror routine clinical practice as far as possible, so that the results will be widely applicable and relevant to determining the place of carotid stenting in clinical practice in the future.

Carotid Stenosis↗
PubMed2005

Applying a phase II futility study design to therapeutic stroke trials.

BACKGROUND AND PURPOSE: Most large, randomized phase III efficacy trials of therapeutic agents in ischemic stroke have failed to find treatment benefit. We determined whether some phase III studies could have been avoided if preceded by smaller single-arm phase II studies to evaluate the futility of proceeding to phase III. METHODS: To provide examples of the application of phase II methodology, we obtained primary outcome data for the active treatment group of 6 phase III ischemic stroke therapy trials. For each study, we estimated the sample size number required for a multistage single-arm study using parameters specified in the original study. We evaluated outcome data for the first number of subjects in the phase III study treatment arm ordered by enrollment dates. We compared the proportion of favorable outcomes to prespecified stopping criteria derived from a single-arm phase II futility design. If the observed proportion of favorable outcomes was less than the stopping criterion, we declared the treatment not sufficiently effective to warrant further evaluation in phase III. RESULTS: We identified 3 trials as futile in phase II; none of 3 showed treatment efficacy in phase III. In the 3 remaining phase II trials in which we did not show futility, one showed efficacy in phase III. CONCLUSIONS: Single-arm phase II futility studies have been underused in stroke research, but provide a strategy for discarding treatments likely to be ineffective in phase III trials.

Clinical Trials as Topic↗
PubMed2002

Comparisons of the variability of three markers of the human circadian pacemaker.

A circadian pacemaker within the central nervous system regulates the approximately 24-h physiologic rhythms in sleep cycles, hormone secretion, and other physiologic functions. Because the pacemaker cannot be examined directly in humans, markers of pacemaker function must be used to study the pacemaker and its response to environmental stimuli. Core body temperature (CBT), plasma cortisol, and plasma melatonin are three marker variables frequently used to estimate the phase of the human pacemaker. Measurements of circadian phase using markers can contain variability due to the circadian pacemaker itself, the intrinsic variability of the marker relative to the pacemaker, the method of analysis of the marker, and the marker assay. For this report, we compared the mathematical variability of a number of methods of identifying circadian phase from CBT, plasma cortisol, and plasma melatonin data collected in a protocol in which pacemaker variability was minimized using low light levels and regular timing of both the light pattern and the rest/activity schedule. We hoped to assess the relative variabilities of the different physiological markers and the analysis methods. Methods were based on the crossing of an absolute threshold, on the crossing of a relative threshold, or on fitting a curve to all data points. All methods of calculating circadian phase from plasma melatonin data were less variable than those calculated using CBT or cortisol data. The standard deviation for the phase estimates using CBT data was 0.78 h, using cortisol data was 0.65 h, and for the eight analysis methods using melatonin data was 0.23 to 0.35 h. While the variability for these markers might be different for other subject populations and/or less stringent study conditions, assessment of the intrinsic variability of the different calculations of circadian phase can be applied to allow inference of the statistical significance of phase and phase shift calculations, as well as estimation of sample size or statistical power for the number of subjects within an experimental protocol.

Adolescent↗
PubMedDate not supplied

Factor structure and reliability of the Alzheimer's Disease Assessment Scale in a multicenter trial with linopirdine.

The Alzheimer's Disease Assessment Scale (ADAS) has assumed a primary role in assessment of treatment responses in large-scale multicenter trials of drugs being evaluated for treatment of dementia in elderly patients. Data from 280 patients with Alzheimer's disease were analyzed to evaluate factor structure and reliability. Results confirm the presence of three primary factors interpreted as mental status, verbal fluency, and praxis. The presence of a large general factor underlying those more specific dimensions also supports the utility of the composite ADAS cognitive score that has been used as a primary outcome measure in previous drug trials. Test-retest reliability of the factor scores were calculated to be 0.83, 0.78, and 0.87. Test-retest reliability of the composite ADAS cognitive score was 0.90. Statistics useful for estimation of sample sizes for future multicenter trials are provided.

Aged↗
PubMed1993

Design and analysis of studies of the health effects of ozone.

The design and analysis of studies that investigate the effect of exposure to ozone on health outcomes need to define carefully the methods for the assessment of the exposure and to determine precisely which is the outcome of biological relevance. The estimation of sample size for longitudinal studies requires the expected rates of change among the exposed and unexposed, the variance of the outcome, and the correlation of measurements taken within an individual. Methods of analysis whose primary interest is in the combination of cross-sectional studies for the determination of the marginal distribution of the outcome are particularly appropriate for biological processes where the effect of exposure is acute. Conditional models are particularly useful for investigating the effect of changes in exposure on changes in outcome at the individual level. In addition, conditional models incorporate a dampening effect of exposure that may provide a reasonable agreement with several biological mechanisms. The identification of susceptible individuals and the description of the behavior of their outcomes over time may be better accomplished by using the within-individual variance as the outcome of interest. Discrepancies of the within- and between-individual regressions may be suggestive of chronic effects, and methodological research in this area is needed. Studies of the health effects of ozone exposure need to address the incorporation of missing data, measurement error, and the combination of complementary studies.

Acute Disease↗
PubMed1999

Defining incident vertebral deformity: a prospective comparison of several approaches. The Study of Osteoporotic Fractures Research Group.

Vertebral deformities are common and important outcomes in clinical trials and epidemiologic studies of osteoporosis. While several different methods for defining new deformities have been proposed, it is not clear which is best. We used data from serial spine radiographs obtained an average of 3.7 years apart in 7238 women age >/=65 years from the Study of Osteoporotic Fractures to compare several approaches to defining new deformities by morphometry including a fixed percentage reduction in any vertebral height (FIXED%), a change in a summary spinal deformity index, a change in a vertebra from no prevalent deformity at baseline to a deformity at follow-up, as well as several variations of these methods. We compared results of each definition with several clinical correlates, including height loss, back pain, age, baseline bone mineral density, and the presence of a baseline deformity. We also estimated the sample size required for a clinical trial using various cut points. At a given level of incidence, all methods had similar relationships with each of the correlates. Given that similarity, the FIXED% method was simplest and needed no reference data. Using the FIXED% method, a 20-25% vertebral height reduction criterion for deformity maximized the power for a clinical trial. We conclude that all of the morphometric approaches to defining incident deformities have similar relationships to clinical correlates of vertebral deformity, but that use of a fixed percentage reduction in vertebral height is the simplest and most practical. For the FIXED% method, a 20-25% reduction in vertebral height minimizes the sample size required for clinical trials and epidemiologic studies.

Aged↗
PubMed2001

Microsatellite DNA polymorphism and heterozygosity among field and laboratory populations of Anopheles gambiae ss (Diptera: Culicidae).

We compared microsatellite polymorphism at nine loci located on chromosome 3 among two colonies and a field population of Anopheles gambiae sensu stricto Giles mosquitoes. Numbers of microsatellite alleles observed at each locus and mean heterozygosities were drastically reduced among laboratory colonies. Genetic analysis of the field population used in this study revealed an unprecedented frequency of rare alleles (<0.05). In contrast, colony samples revealed large numbers of alleles with frequencies >0.50. Partitioning of field data to assess the impact of rare alleles, null alleles, and sample size on estimates of mean heterozygosity revealed the plasticity of this measurement and suggests that heterozygosity may be reliably estimated from relatively small collections using microsatellites.

Alleles↗
PubMed2004

Image-based computational fluid dynamics: a new paradigm for monitoring hemodynamics and atherosclerosis.

Complex blood flow dynamics are thought to play a key role in the development and treatment of atherosclerosis; however, the exact nature of this role is incompletely understood owing to the practical difficulties associated with measuring important local hemodynamic factors, notably wall shear stresses, in vivo. Only recently has it become possible to consider mapping these hemodynamic factors in a prospective, patient-specific manner via the coupling of in vivo medical imaging and computational fluid dynamics (CFD) modelling. CFD models derived from intravascular ultrasound have already been used to elucidate the role that hemodynamic forces play in mechanical and pharmacological interventions for coronary atherosclerosis. CFD models derived from magnetic resonance imaging and three-dimensional ultrasound provide a less invasive window into more superficial vessels such as the carotid bifurcation, and thus are promising tools for clarifying the role of, and eventually exploiting, purported local geometric and hemodynamic risk factors for atherosclerosis and its response to therapeutic options. Efforts to improve the ease and robustness with which these models are constructed have led to concomitant improvements in accuracy and precision, data for which are presented to facilitate estimation of sample sizes for future studies. Current limitations and anticipated future directions for these powerful new tools are discussed.

Arteriosclerosis↗