Biomedical subjects

Allan Donner

Publications and source records attributed to Allan Donner.

At least 19 recordsLinked to original sources

PubMed2007

Accounting for expected attrition in the planning of community intervention trials.

Trials in which intact communities are the units of randomization are increasingly being used to evaluate interventions which are more naturally administered at the community level, or when there is a substantial risk of treatment contamination. In this article we focus on the planning of community intervention trials in which k communities (for example, medical practices, worksites, or villages) are to be randomly allocated to each of an intervention and a control group, and fixed cohorts of m individuals enrolled in each community prior to randomization. Formulas to determine k or m may be obtained by adjusting standard sample size formulas to account for the intracluster correlation coefficient rho. In the presence of individual-level attrition however, observed cohort sizes are likely to vary. We show that conventional approaches of accounting for potential attrition, such as dividing standard sample size formulas by the anticipated follow-up rate pi or using the average anticipated cohort size m pi, may, respectively, overestimate or underestimate the required sample size when cluster follow-up rates are highly variable, and m or rho are large. We present new sample size estimation formulas for the comparison of two means or two proportions, which appropriately account for variation among cluster follow-up rates. These formulas are derived by specifying a model for the binary missingness indicators under the population-averaged approach, assuming an exchangeable intracluster correlation coefficient, denoted by tau. To aid in the planning of future trials, we recommend that estimates for tau be reported in published community intervention trials.

Canada↗

PubMed2007

The merits of breaking the matches: a cautionary tale.

Matched-pair cluster randomization trials are frequently adopted as the design of choice for evaluating an intervention offered at the community level. However, previous research has demonstrated that a strategy of breaking the matches and performing an unmatched analysis may be more efficient than performing a matched analysis on the resulting data, particularly when the total number of communities is small and the matching is judged as relatively ineffective. The research concerning this question has naturally focused on testing the effect of intervention. However, a secondary objective of many community intervention trials is to investigate the effect of individual-level risk factors on one or more outcome variables. Focusing on the case of a continuous outcome variable, we show that the practice of performing an unmatched analysis on data arising from a matched-pair design can lead to bias in the estimated regression coefficient, and a corresponding test of significance which is overly liberal. However, for large-scale community intervention trials, which typically recruit a relatively small number of large clusters, such an analysis will generally be both valid and efficient. We also consider other approaches to testing the effect of an individual-level risk factor in a matched-pair cluster randomization design, including a generalized linear model approach that preserves the matching, a two-stage cluster-level analysis, and an approach based on generalized estimating equations.

Asthma↗

PubMed2006

Caesarean delivery rates and pregnancy outcomes: the 2005 WHO global survey on maternal and perinatal health in Latin America.

BACKGROUND: Caesarean delivery rates continue to increase worldwide. Our aim was to assess the association between caesarean delivery and pregnancy outcome at the institutional level, adjusting for the pregnant population and institutional characteristics. METHODS: For the 2005 WHO global survey on maternal and perinatal health, we assessed a multistage stratified sample, comprising 24 geographic regions in eight countries in Latin America. We obtained individual data for all women admitted for delivery over 3 months to 120 institutions randomly selected from of 410 identified institutions. We also obtained institutional-level data. FINDINGS: We obtained data for 97,095 of 106,546 deliveries (91% coverage). The median rate of caesarean delivery was 33% (quartile range 24-43), with the highest rates of caesarean delivery noted in private hospitals (51%, 43-57). Institution-specific rates of caesarean delivery were affected by primiparity, previous caesarean delivery, and institutional complexity. Rate of caesarean delivery was positively associated with postpartum antibiotic treatment and severe maternal morbidity and mortality, even after adjustment for risk factors. Increase in the rate of caesarean delivery was associated with an increase in fetal mortality rates and higher numbers of babies admitted to intensive care for 7 days or longer even after adjustment for preterm delivery. Rates of preterm delivery and neonatal mortality both rose at rates of caesarean delivery of between 10% and 20%. INTERPRETATION: High rates of caesarean delivery do not necessarily indicate better perinatal care and can be associated with harm.

Adolescent↗

PubMed2006

Lessons and implications from a mass immunization campaign in squatter settlements of Karachi, Pakistan: an experience from a cluster-randomized double-blinded vaccine trial [NCT00125047].

OBJECTIVE: To determine the safety and logistic feasibility of a mass immunization strategy outside the local immunization program in the pediatric population of urban squatter settlements in Karachi, Pakistan. METHODS: A cluster-randomized double blind preventive trial was launched in August 2003 in 60 geographic clusters covering 21,059 children ages 2 to 16 years. After consent was obtained from parents or guardians, eligible children were immunized parenterally at vaccination posts in each cluster with Vi polysaccharide or hepatitis A vaccine. Safety, logistics, and standards were monitored and documented. RESULTS: The vaccine coverage of the population was 74% and was higher in those under age 10 years. No life-threatening serious adverse events were reported. Adverse events occurred in less than 1% of all vaccine recipients and the main reactions reported were fever and local pain. The proportion of adverse events in Vi polysaccharide and hepatitis A recipients will not be known until the end of the trial when the code is broken. Throughout the vaccination campaign safe injection practices were maintained and the cold chain was not interrupted. Mass vaccination in slums had good acceptance. Because populations in such areas are highly mobile, settlement conditions could affect coverage. Systemic reactions were uncommon and local reactions were mild and transient. Close community involvement was pivotal for information dissemination and immunization coverage. CONCLUSION: This vaccine strategy described together with other information that will soon be available in the area (cost/effectiveness, vaccine delivery costs, etc) will make typhoid fever control become a reality in the near future.

Journal Article↗

PubMed2006

The prevalence of stillbirths: a systematic review.

BACKGROUND: Stillbirth rate is an important indicator of access to and quality of antenatal and delivery care. Obtaining overall estimates across various regions of the world is not straightforward due to variation in definitions, data collection methods and reporting. METHODS: We conducted a systematic review of a range of pregnancy-related conditions including stillbirths and performed meta-analysis of the subset of studies reporting stillbirth rates. We examined variation across rates and used meta-regression techniques to explain observed variation. RESULTS: We identified 389 articles on stillbirth prevalence among the 2580 included in the systematic review. We included 70 providing 80 data sets from 50 countries in the meta-analysis. Pooled prevalence rates show variation across various subgroup categories. Rates per 100 births are higher in studies conducted in less developed country settings as compared to more developed (1.17 versus 0.50), of inadequate quality as compared to adequate (1.12 versus 0.66), using sub-national sample as compared to national (1.38 versus 0.68), reporting all stillbirths as compared to late stillbirths (0.95 versus 0.63), published in non-English as compared to English (0.91 versus 0.59) and as journal articles as compared to non-journal (1.37 versus 0.67). The results of the meta-regression show the significance of two predictor variables - development status of the setting and study quality - on stillbirth prevalence. CONCLUSION: Stillbirth prevalence at the community level is typically less than 1% in more developed parts of the world and could exceed 3% in less developed regions. Regular reviews of stillbirth rates in appropriately designed and reported studies are useful in monitoring the adequacy of care. Systematic reviews of prevalence studies are helpful in explaining sources of variation across rates. Exploring these methodological issues will lead to improved standards for assessing the burden of reproductive ill-health.

Journal Article↗

PubMed2006

The merits of testing Hardy-Weinberg equilibrium in the analysis of unmatched case-control data: a cautionary note.

Testing for departures from the assumption of Hardy-Weinberg equilibrium (HWE) has been widely recommended as a preliminary step in the analysis of genetic case-control studies. Some authors suggest using a two-stage procedure in which gene/disease associations are ultimately evaluated using either the Pearson chi-square procedure or the Cochran-Armitage test for trend. Other authors go further and encourage investigators to discard data that are in violation of HWE, essentially using the test as a tool for identifying genotyping errors. In this paper we show that 1) testing for HWE should not be used as a tool to identify genotyping errors; and 2) it is not necessary, and possibly even harmful, to test the HWE assumption before testing for association between alleles and disease. Instead one should inherently account for deviations from HWE with an adjusted chi-square test statistic, a procedure which in the present context is identical to the trend test. Examples from previous reports are used to illustrate the methodology.

Case-Control Studies↗

PubMed2006

The feasibility of a school-based VI polysaccharide vaccine mass immunization campaign in Hue City, central Vietnam: streamlining a typhoid fever preventive strategy.

We report the coverage, safety, and logistics of a school-based typhoid fever immunization campaign that took place in Hue City, central Vietnam; a typhoid fever endemic area. A cluster-randomized evaluation-blinded controlled trial was designed where 68 schools (cluster) were randomly allocated the single dose Vi polysaccharide vaccine (Typherix) or the active control hepatitis A vaccine (Havrix). A safety surveillance system was implemented. A total of 32,267 children were immunized with a coverage of 57.5%. Strong predictors for vaccination were attending primary schools, peri-urban location of the school, and low family income. Human resources were mainly schoolteachers and the campaign was completed in about 1 month. Most adverse events reported were mild. Safe injection and safe sharp-waste disposal practices were followed. A typhoid fever school-based immunization campaign was safe and logistically possible. Coverage was moderate and can be interpreted as the minimum that could have been achievable because individual written informed consent procedures were sought for the first time in Hue City and the trial nature of the campaign. The lessons learned, together with cost-effectiveness results to be obtained by the end of follow-up period, will hopefully accelerate the introduction of Vi typhoid fever vaccine in Vietnam.

Adolescent↗

PubMed2005

Efficacy of an extract of North American ginseng containing poly-furanosyl-pyranosyl-saccharides for preventing upper respiratory tract infections: a randomized controlled trial.

BACKGROUND: Upper respiratory tract infections are a major source of morbidity throughout the world. Extracts of the root of North American ginseng (Panax quinquefolium) have been found to have the potential to modulate both natural and acquired immune responses. We sought to examine the efficacy of an extract of North American ginseng root in preventing colds. METHODS: We conducted a randomized, double-blind, placebo-controlled study at the onset of the influenza season. A total of 323 subjects 18-65 years of age with a history of at least 2 colds in the previous year were recruited from the general population in Edmonton, Alberta. The participants were instructed to take 2 capsules per day of either the North American ginseng extract or a placebo for a period of 4 months. The primary outcome measure was the number of Jackson-verified colds. Secondary variables measured included symptom severity, total number of days of symptoms and duration of all colds. Cold symptoms were scored by subjects using a 4-point scale. RESULTS: Subjects who did not start treatment were excluded from the analysis (23 in the ginseng group and 21 in the placebo group), leaving 130 in the ginseng group and 149 in the placebo group. The mean number of colds per person was lower in the ginseng group than in the placebo group (0.68 [standard deviation (SD) 0.82] v. 0.93 [SD 0.91], difference 0.25%, 95% confidence interval [CI] 0.04-0.45). The proportion of subjects with 2 or more Jackson-verified colds during the 4-month period (10.0% v. 22.8%, 12.8% difference, 95% CI 4.3-21.3) was significantly lower in the ginseng group than in the placebo group, as were the total symptom score (77.5 [SD 84.6] v. 112.3 [SD 102.5], difference 1.5%, 95% CI 1.2-2.0) and the total number of days cold symptoms were reported (10.8 [SD 9.7] v. 16.5 [SD 13.8] days, difference 1.6%, 95% CI 1.3-2.0) for all colds. INTERPRETATION: Ingestion of a poly-furanosyl-pyranosyl-saccharide-rich extract of the roots of North American ginseng in a moderate dose over 4 months reduced the mean number of colds per person, the proportion of subjects who experienced 2 or more colds, the severity of symptoms and the number of days cold symptoms were reported.

Adolescent↗

PubMed2005

A mass vaccination campaign targeting adults and children to prevent typhoid fever in Hechi; expanding the use of Vi polysaccharide vaccine in southeast China: a cluster-randomized trial.

BACKGROUND: One of the goals of this study was to learn the coverage, safety and logistics of a mass vaccination campaign against typhoid fever in children and adults using locally produced typhoid Vi polysaccharide (PS) and group A meningococcal PS vaccines in southern China. METHODS: The vaccination campaign targeted 118,588 persons in Hechi, Guangxi Province, aged between 5 to 60 years, in 2003. The study area was divided into 107 geographic clusters, which were randomly allocated to receive one of the single-dose parenteral vaccines. All aspects regarding vaccination logistics, feasibility and safety were documented and systematically recorded. Results of the logistics, feasibility and safety are reported. RESULTS: The campaign lasted 5 weeks and the overall vaccination coverage was 78%. On average, the 30 vaccine teams gave immunizations on 23 days. Vaccine rates were higher in those aged < or = 15 years (90%) than in adolescents and young adults (70%). Planned mop-up activities increased the coverage by 17%. The overall vaccine wastage was 11%. The cold chain was maintained and documented. 66 individuals reported of adverse events out of all vaccinees, where fever (21%), malaise (19%) and local redness (19%) were the major symptoms; no life-threatening event occurred. Three needle-sharp events were reported. CONCLUSION: The mass immunization proved feasible and safe, and vaccine coverage was high. Emphasis should be placed on: injection safety measures, community involvement and incorporation of mop-up strategies into any vaccination campaign. School-based and all-age Vi mass immunizations programs are potentially important public health strategies for prevention of typhoid fever in high-risk populations in southern China.

Adolescent↗

PubMed2005

A multi-country cluster randomized controlled effectiveness evaluation to accelerate the introduction of Vi polysaccharide typhoid vaccine in developing countries in Asia: rationale and design.

Phase-III vaccine efficacy trials typically employ individually randomized designs intended to ensure that measurements of vaccine protective efficacy reflect only direct vaccine effects. As a result, decisions about introducing newly licensed vaccines into public health programmes often fail to consider the substantially greater protection that may occur when a vaccine is deployed in public health programmes, due to the combination of direct plus indirect vaccine protective effects. Vaccine total protection can be better evaluated with cluster randomized trials. Such a design was considered to generate policy relevant data to accelerate the rationale introduction of the licensed typhoid fever Vi polysaccharide (PS) vaccine in Asia by the Diseases of the Most Impoverished (DOMI) typhoid fever programme. The DOMI's programme multi-country study is one of the largest cluster randomized vaccine trials ever mounted in Asia, which includes approximately 200,000 individuals. Its main objective is to determine the effectiveness of a licensed Vi PS vaccine. The rationale and design of this study are discussed. Preliminary results are presented that determined the final planning of the trial before immunization. Important methodological and practical issues regarding vaccine cluster randomized designs are illustrated.

Adolescent↗

PubMed2005

Group sequential methods for cluster randomization trials with binary outcomes.

BACKGROUND: Cluster randomization trials in which intact social units are randomly assigned to different intervention groups have become very popular in recent years, particularly for the evaluation of innovations in the delivery of health care. An extensive literature dealing with the associated methodological challenges has also appeared. Although the monitoring of such trials using formal stopping rules is clearly indicated when the outcomes are irreversible and individual-level data are available sequentially, simple and reliable statistical methods that may be used for this purpose are currently not available. PURPOSE: To investigate the validity of standard group sequential methods when applied to cluster randomization trials having binary outcomes. METHODS: The large sample distributions for each of five test statistics computed from sequentially accumulated data are derived. A simulation study is performed to evaluate the finite sample properties of these statistics when applied to the interim analysis of cluster randomization trials. Data from the World Health Organization antenatal care trial are used to illustrate the methods. RESULTS: Each of the joint distributions is shown to be characterized by a covariance structure that asymptotically satisfies an independent increments structure, a foundation that simplifies group sequential methods. The simulation study reveals that four of the five test statistics evaluated provide satisfactory performance with as few as 10 clusters allocated to each of two interventions. LIMITATIONS: The applicability of our results to effect estimation following a group sequential cluster randomization trial is not investigated, although a theoretical foundation which may be used for this purpose is presented. CONCLUSIONS: Standard group sequential methods can be applied to cluster randomization trials when interim analyses are warranted.

Clinical Trials as Topic↗

PubMed2004

Mandatory second opinion to reduce rates of unnecessary caesarean sections in Latin America: a cluster randomised controlled trial.

BACKGROUND: Latin America has a high rate of caesarean sections. We tested the hypothesis that a hospital policy of mandatory second opinion, based on the best existing scientific evidence, reduces the hospital caesarean section rate by 25%, without increasing maternal and perinatal morbidity and mortality. METHODS: 36 hospitals in Argentina (18), Brazil (eight), Cuba (four), Guatemala (two), and Mexico (four), were randomly assigned to intervention or control in a matched pair design. All physicians in the intervention hospitals deciding a non-emergency caesarean section had to follow a policy of mandatory second opinion. The primary outcome was the overall caesarean section rate in the hospitals after a 6-month implementation period. We also assessed women's satisfaction with labour and delivery care and physicians'acceptance of the second opinion policy. FINDINGS: A total of 34 hospitals attending 149?276 deliveries were randomised and completed the protocol. The mandatory second opinion policy was associated with a small but significant reduction in rates of caesarean section (relative rate reduction 7.3%; 95% CI 0.2-14.5), mostly in intrapartum sections (12.6%; 0.6-24.7). Other maternal and neonatal outcomes and women's perceptions and satisfaction with the process of care were similarly distributed between the groups. INTERPRETATION: In hospitals applying this policy of second opinion, 22 intrapartum caesarean sections could be prevented per 1000 deliveries, without affecting maternal or perinatal morbidity, and without affecting mothers' satisfaction with the care process.

Adult↗

PubMed2004

A simple alternative confidence interval for the difference between two proportions.

The difference between two proportions is often the focus of interest in prospective comparative studies such as randomized controlled trials that have a binary outcome. Consequently, interval estimation for this parameter has received considerable attention in the literature. A hybrid procedure resulting from combining two sets of confidence limits for a single proportion as proposed by Newcombe has been previously recommended for this purpose because of its superior properties and relative simplicity. In this paper, we propose a simple alternative approach based on Fisher's z transformation. The results of an exact evaluation study show that this new procedure performs as well as Newcombe's procedure in terms of percent coverage and expected confidence interval width. Several examples are presented.

Algorithms↗

PubMed2004

Confidence interval estimation of the intraclass correlation coefficient for binary outcome data.

We obtain closed-form asymptotic variance formulae for three point estimators of the intraclass correlation coefficient that may be applied to binary outcome data arising in clusters of variable size. Our results include as special cases those that have previously appeared in the literature (Fleiss and Cuzick, 1979, Applied Psychological Measurement 3, 537-542; Bloch and Kraemer, 1989, Biometrics 45, 269-287; Altaye, Donner, and Klar, 2001, Biometrics 57, 584-588). Simulation results indicate that confidence intervals based on the estimator proposed by Fleiss and Cuzick provide coverage levels close to nominal over a wide range of parameter combinations. Two examples are presented.

Biometry↗

PubMed2004

Methods for the statistical analysis of binary data in split-cluster designs.

Split-cluster designs are frequently used in the health sciences when naturally occurring clusters such as multiple sites or organs in the same subject are assigned to different treatments. However, statistical methods for the analysis of binary data arising from such designs are not well developed. The purpose of this article is to propose and evaluate a new procedure for testing the equality of event rates in a design dividing each of k clusters into two segments having multiple sites (e.g., teeth, lesions). The test statistic proposed is a generalization of a previously published procedure based on adjusting the standard Pearson chi-square statistic, but can also be derived as a score test using the approach of generalized estimating equations.

Anti-Infective Agents, Local↗

PubMed2004

Flexible client-driven in-home case management: an option to consider.

Changes in health services and care needs have created high demand for case management of in-home services. To address this challenge, several models of case management have been used. Evaluations to date suggest that clients need different approaches for different circumstances at different times to optimize cost-effectiveness. Accordingly, one Canadian home care program adopted flexible client-driven case management engaging clients as partners in flexibly selecting either an integrated team, consumer-managed or brokerage model of case management in keeping with their preferences and abilities. Using an exploratory, multimeasure quasi-experimental design, a generic model of program evaluation, and both quantitative and qualitative methods, researchers identified challenges in implementing this intervention, policy impediments the clients characteristically in each of the three case management models, and client, provider, and caregiver outcomes of flexible, client-driven care. While further longitudinal investigation is needed findings suggest several important considerations for those interested in this option for care management. Alternative case management models do attract different client groups, and having a choice does not alter care costs or outcomes. Flexible client-driven case management may be experienced positively by case managers and other providers.

Aged↗

PubMed2004

Pitfalls of and controversies in cluster randomization trials.

It is now well known that standard statistical procedures become invalidated when applied to cluster randomized trials in which the unit of inference is the individual. A resulting consequence is that researchers conducting such trials are faced with a multitude of design choices, including selection of the primary unit of inference, the degree to which clusters should be matched or stratified by prognostic factors at baseline, and decisions related to cluster subsampling. Moreover, application of ethical principles developed for individually randomized trials may also require modification. We discuss several topics related to these issues, with emphasis on the choices that must be made in the planning stages of a trial and on some potential pitfalls to be avoided.

Bias↗

PubMed2003

Meta-analyses of cluster randomization trials. Power considerations.

A commonly cited purpose for conducting a meta-analysis of randomized trials is to increase the statistical power for detecting the effect of an intervention on a specified set of endpoints. At the same time, it also has been noted by several authors that many large-scale cluster randomization trials have not had the power to detect small or even moderate effect sizes. The loss of efficiency associated with cluster randomization relative to individual randomization, and the frequent failure of investigators to take this loss of efficiency into account at the planning stage of a trial, undoubtedly contributes to this problem. In this article, the authors present an approach that may be used to estimate the power of a planned meta-analysis that includes trials that are cluster randomized. Two examples are presented.

Cluster Analysis↗