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Biomedical subjects

Andrew R Willan

Publications and source records attributed to Andrew R Willan.

At least 19 recordsLinked to original sources
PubMed2007

Expected value of information and decision making in HTA.

Decision makers within a jurisdiction facing evidence of positive but uncertain incremental net benefit of a new health care intervention have viable options where no further evidence is anticipated to:(1)adopt the new intervention without further evidence;(2)adopt the new intervention and undertake a trial; or(3)delay the decision and undertake a trial.Value of information methods have been shown previously to allow optimal design of clinical trials in comparing option (2) against option (1), by trading off the expected value and cost of sample information. However, this previous research has not considered the effect of cost of reversal on expected value of information in comparing these options. This paper demonstrates that, where a new intervention is adopted, the expected value of information is reduced under optimal decision making with costs of reversing decisions. Further, the paper shows that comparing expected net gain of optimally designed trials for option (2) vs (1) conditional on cost of reversal, and (3) vs (1) conditional on opportunity cost of delay allow systematic identification of an optimal decision strategy and trial design.

Clinical Trials as Topic↗
PubMed2006

Health status measurements at diagnosis as predictors of survival among adults with brain tumors.

PURPOSE: The intent of this study was to determine whether baseline measures of functional capacity and performance could be used to predict survival in adults following the diagnosis of brain tumors. PATIENTS AND METHODS: Comprehensive health status and health-related quality of life (HRQL) were measured using the Health Utilities Index (HUI; McMaster University, Hamilton, Canada) system by a self-assessment questionnaire in a survey of 100 consecutive patients. The Karnofsky Performance Score (KPS) and Folstein's Mini-Mental State Examination (MMSE) scores were measured by a physician blinded to the HUI results. The patients were observed for up to 5 years to recorded dates of death. RESULTS: An HUI questionnaire was completed for 93% of the patients and 69% died within 5 years of assessment. The HUI revealed a burden of morbidity and complexity of disability that far exceeded that reported for the general population. KPS and MMSE correlated strongly with each other (r = 0.52; P < .001). A decrease of 0.1 units in HUI Mark 2 (HUI2) self-care single-attribute utility score was associated with an increased hazard of death of 30% (P = .023) for patients with low-grade tumors (n=25). For patients with high-grade tumors (n=56), a 10 unit decrease in the KPS, a 5 unit decrease in MMSE, and a 0.1 decrease in HUI Mark 3 (HUI3) speech and dexterity single-attribute scores were associated with an increased hazard of death of 20% (P = .022), 26% (P = .015), 36% (P = .021), and 18% (P = .035), respectively. CONCLUSION: Scores derived from the measurement of HRQL following diagnosis can predict survival in adults with brain tumors.

Adult↗
PubMed2006

The costs of planned cesarean versus planned vaginal birth in the Term Breech Trial.

BACKGROUND: The Term Breech Trial compared the safety of planned cesarean and planned vaginal birth for breech presentations at term. The combined outcome of perinatal or neonatal death and serious neonatal morbidity was found to be significantly lower among babies delivered by planned cesarean section. In this study we conducted a cost analysis of the 2 approaches to breech presentations at delivery. METHODS: We used a third-party-payer (i.e., Ministry of Health) perspective. We included all costs for physician services and all hospital-related costs incurred by both the mother and the infant. We collected health care utilization and outcomes for all study participants during the trial. We used only the utilization data from countries with low national rates of perinatal death (< or = 20/1000). Seven hospitals across Canada (4 teaching and 3 community centres) were selected for unit cost calculations. RESULTS: The estimated mean cost of a planned cesarean was significantly lower than that of a planned vaginal birth (7165 dollars v. 8042 dollars per mother and infant; mean difference -877 dollars, 95% credible interval -1286 dollars to -473 dollars). The estimated mean cost of a planned cesarean was lower than that of a planned vaginal birth for both women having a first birth (7255 dollars v. 8440 dollars) and women having had at least one prior birth (7071 dollars v. 7559 dollars). Although the treatment effect was largest in the subgroup of women having their first child, there was no statistically significant interaction between treatment and parity since the 95% credible intervals for difference in treatment effects between parity equalling zero and parity of one or greater all include zero. INTERPRETATION: Planned cesarean section was found to be less costly than planned vaginal birth for the singleton fetus in a breech presentation at term in the Term Breech Trial.

Adult↗
PubMed2006

Pediatric stroke initiatives and preliminary studies: What is known and what is needed?

Cerebrovascular disorders are increasingly recognized as important causes of mortality and morbidity in the pediatric population. However, there have been no clinical trials performed to assess the safety and tolerability of acute interventions or secondary preventative treatments. In 2002, the International Pediatric Stroke Study was launched to create a network of investigators, with an interest in developing standards of practice, as well as design and implement the first-ever clinical trials in pediatric stroke. This article reviews existing studies in pediatric stroke epidemiology, risk factors, outcomes, as well as experience with antithrombotic trials in children. From there, current and future initiatives in the development of clinical trials in pediatric stroke are evaluated.

Child↗
PubMed2006

Perspectives on the management of the short cervix identified by transvaginal ultrasound during pregnancy: an update for Canadian obstetrical caregivers.

A shortened cervix is often considered to be equivalent to cervical insufficiency, and a cerclage may be offered as an intervention to prolong pregnancy; however, we may not be differentiating between true cervical insufficiency and intrauterine causes of cervical shortening. A recent meta-analysis found no significant reduction in preterm birth < 35 weeks' gestation in women with cerclage compared with no cerclage in the total population of women studied. However, there was a potentially significant reduction in preterm birth < 35 weeks among women with a singleton pregnancy (relative risk [RR] 0.74; 95% confidence intervals [CI] 0.57-0.96), with a singleton pregnancy and a previous preterm birth (RR 0.61; 95% CI 0.40-0.92), and with a singleton pregnancy with a previous mid-trimester loss (RR 0.57; 95% CI 0.33-0.99). An increase was found in preterm birth among twin gestations with cerclage placed for a shortened cervix on transvaginal ultrasound (RR 2.15; 95% CI 1.15-4.01). This unexpected finding underscores the possibility of harm with this intervention. This intervention deserves further study. A national registry or database would allow us to identify women who may benefit more significantly from cerclage by collecting data on possible confounding effects such as concomitant intrauterine infection or placental disease.

Canada↗
PubMed2006

Economic evaluation of rivastigmine in patients with Parkinson's disease dementia.

BACKGROUND: The positive results of a randomised clinical trial of rivastigmine in patients with dementia associated with Parkinson's disease have been published recently. Patient-level healthcare utilisation data were also collected, and this report is the economic evaluation based on these data. OBJECTIVE: To determine the cost effectiveness of rivastigmine 3-12 mg/day in patients in whom mild to moderate dementia developed at least 2 years after they received a clinical diagnosis of Parkinson's disease. METHODS: A cost-effectiveness analysis was performed by applying Canadian and UK cost weights (year 2004 values) to healthcare utilisation data collected prospectively during a randomised, double-blind, multinational, 24-week trial of rivastigmine 3-12 mg/day (n = 362) versus placebo (n = 179). Patients were > or =50 years of age, had a Mini-Mental State Examination (MMSE) score of between 20 and 24 and had contact with a responsible caregiver at least 3 days a week.Quality-adjusted survival time, transformed from MMSE scores, was the measure of effectiveness. Caregiver costs included paid and unpaid time, and direct costs included concomitant medications, outpatient care, hospitalisations, long-term care and study medications. Analysis was conducted from a societal perspective with a time horizon of 24 weeks. RESULTS: Consistent with the improvement in clinical outcomes, there was an observed increase in quality-adjusted survival time in the rivastigmine arm of 2.81 quality-adjusted life-days (two-sided p-value 0.13 [90% CI -0.243, 5.86]). Using Canadian price weights, there was an observed increase in cost in the rivastigmine arm of Can 55.76 dollars(two-sided p-value 0.98 [90% CI -3431, 3543]), with a resulting incremental cost-effectiveness ratio of Can 7429 dollars per QALY. Using UK price weights, there was an observed decrease in cost in the rivastigmine arm of pound 26.18 (two-sided p-value 0.99 [90% CI -2407, 2355]). CONCLUSION: Although no between-treatment differences in cost were seen, the small sample size, highly variable cost distributions and short time horizon prevent us from making strong conclusions with regard to the effect of rivastigmine on total costs and, by inference, on cost effectiveness.

Aged↗
PubMed2006

'Lost in translation': accounting for between-country differences in the analysis of multinational cost-effectiveness data.

Cost-effectiveness analysis has gained status over the last 15 years as an important tool for assisting resource allocation decisions in a budget-limited environment such as healthcare. Randomised (multicentre) multinational controlled trials are often the main vehicle for collecting primary patient-level information on resource use, cost and clinical effectiveness associated with alternative treatment strategies. However, trial-wide cost effectiveness results may not be directly applicable to any one of the countries that participate in a multinational trial, requiring some form of additional modelling to customise the results to the country of interest. This article proposes an algorithm to assist with the choice of the appropriate analytical strategy when facing the task of adapting the study results from one country to another. The algorithm considers different scenarios characterised by: (a) whether the country of interest participated in the trial; and (b) whether individual patient-level data (IPD) from the trial are available. The analytical options available range from the use of regression-based techniques to the application of decision-analytic models. Decision models are typically used when the evidence base is available exclusively in summary format whereas regression-based methods are used mainly when the country of interest actively recruited patients into the trial and there is access to IPD (or at least country-specific summary data). Whichever method is used to reflect between-country variability in cost-effectiveness data, it is important to be transparent regarding the assumptions made in the analysis and (where possible) assess their impact on the study results.

Cost-Benefit Analysis↗
PubMed2005

Cost-effectiveness analysis for multinational clinical trials.

Clinical trials of cost-effectiveness are often conducted in more than one country. The two most common ways of dealing with the multinational nature of the data are either to calculate a pooled estimate or to stratify results by country. Since the between-country heterogeneity in costs is potentially substantial, pooled estimates may be difficult to interpret for any one country. Policy decisions are often made at a national level, and so country-specific results are important. However, country-specific analyses will be based on fewer patients and will often fail to provide adequate precision for statistical analyses. Shrinkage estimation is a compromise between these two methods and has been used successfully in other fields. These estimates are country-specific yet less variable than those derived through a subgroup approach. Univariate and multivariate shrinkage estimators for costs and effects are proposed, then compared with one another and to the traditional methods in a simulation study. The methods are illustrated using data from a multinational trial evaluating the cost-effectiveness of three thrombolytic drug regimens in patients with acute myocardial infarction.

Clinical Trials as Topic↗
PubMed2005

The value of information and optimal clinical trial design.

Traditional sample size calculations for randomized clinical trials depend on somewhat arbitrarily chosen factors, such as type I and II errors. Type I error, the probability of rejecting the null hypothesis of no difference when it is true, is most often set to 0.05, regardless of the cost of such an error. In addition, the traditional use of 0.2 for the type II error means that the money and effort spent on the trial will be wasted 20 per cent of the time, even when the true treatment difference is equal to the smallest clinically important one and, again, will not reflect the cost of making such an error. An effectiveness trial (otherwise known as a pragmatic trial or management trial) is essentially an effort to inform decision-making, i.e. should treatment be adopted over standard? As such, a decision theoretic approach will lead to an optimal sample size determination. Using incremental net benefit and the theory of the expected value of information, and taking a societal perspective, it is shown how to determine the sample size that maximizes the difference between the cost of doing the trial and the value of the information gained from the results. The methods are illustrated using examples from oncology and obstetrics.

Bayes Theorem↗
PubMed2005

Regression methods for cost-effectiveness analysis with censored data.

A system of seemingly unrelated regression equations is proposed for prognostic factor adjustment and subgroup analysis when comparing two groups in a cost-effectiveness analysis with censored data. Because of the induced dependent censoring on costs and quality-adjusted survival, inverse probability weighting is employed for parameter estimation. The method is illustrated with data from two recent examples using both survival time and quality-adjusted survival time as the measures of effectiveness.

Amiodarone↗
PubMed2005

Country specific cost comparisons from multinational clinical trials using empirical Bayesian shrinkage estimation: the Canadian ASSENT-3 economic analysis.

The growing number of multinational clinical trials in which patient-level health care resource data are collected have raised the issue of which is the best approach for making inference for individual countries with respect to the between-treatment difference in mean cost. We describe and discuss the relative merits of three approaches. The first uses the random effects pooled estimate from all countries to estimate the difference for any particular country. The second approach estimates the difference using only the data from the specific country in question. Using empirical Bayes estimation a third approach estimates the country-specific difference using a variance-weighted linear sum of the estimates provided by the other two approaches. The approaches are illustrated and compared using the data from the ASSENT-3 trial.

Abciximab↗
PubMed2005

Conducting economic evaluations alongside multinational clinical trials: toward a research consensus.

Demand for economic evaluations in multinational clinical trials is increasing, but there is little consensus about how such studies should be conducted and reported. At a workshop in Durham, North Carolina, we sought to identify areas of agreement about how the primary findings of economic evaluations in multinational clinical trials should be generated and presented. In this paper, we propose a framework for classifying multinational economic evaluations according to (a) the sources of an analyst's estimates of resource use and clinical effectiveness and (b) the analyst's method of estimating costs. We review existing studies in the cardiology literature in the context of the proposed framework. We then describe important methodological and practical considerations in conducting multinational economic evaluations and summarize the advantages and disadvantages of each approach. Finally, we describe opportunities for future research. Delineation of the various approaches to multinational economic evaluation may assist researchers, peer reviewers, journal editors, and decision makers in evaluating the strengths and limitations of particular studies.

Clinical Trials as Topic↗
PubMed2005

Randomized controlled trial of hands-and-knees positioning for occipitoposterior position in labor.

BACKGROUND: Hands-and-knees positioning during labor has been recommended on the theory that gravity and buoyancy may promote fetal head rotation to the anterior position and reduce persistent back pain. A Cochrane review found insufficient evidence to support the effectiveness of this intervention during labor. The purpose of this study was to evaluate the effect of maternal hands-and-knees positioning on fetal head rotation from occipitoposterior to occipitoanterior position, persistent back pain, and other perinatal outcomes. METHODS: Thirteen labor units in university-affiliated hospitals participated in this multicenter randomized, controlled trial. Study participants were 147 women laboring with a fetus at >or=37 weeks' gestation and confirmed by ultrasound to be in occipitoposterior position. Seventy women were randomized to the intervention group (hands-and-knees positioning for at least 30 minutes over a 1-hour period during labor) and 77 to the control group (no hands-and-knees positioning). The primary outcome was occipitoanterior position determined by ultrasound following the 1-hour study period and the secondary outcome was persistent back pain. Other outcomes included operative delivery, fetal head position at delivery, perineal trauma, Apgar scores, length of labor, and women's views with respect to positioning. RESULTS: Women randomized to the intervention group had significant reductions in persistent back pain. Eleven women (16%) allocated to use hands-and-knees positioning had fetal heads in occipitoanterior position following the 1-hour study period compared with 5 (7%) in the control group (relative risk 2.4; 95% CI 0.88-6.62; number needed to treat 11). Trends toward benefit for the intervention group were seen for several other outcomes, including operative delivery, fetal head position at delivery, 1-minute Apgar scores, and time to delivery. CONCLUSIONS: Maternal hands-and-knees positioning during labor with a fetus in occipitoposterior position reduces persistent back pain and is acceptable to laboring women. Given this evidence, hands-and-knees positioning should be offered to women laboring with a fetus in occipitoposterior position in the first stage of labor to reduce persistent back pain. Although this study demonstrates trends toward improved birth outcomes, further trials are needed to determine if hands-and-knees positioning promotes fetal head rotation to occipitoanterior and reduces operative delivery.

Adolescent↗
PubMed2005

Asthma in remission: can relapse in early adulthood be predicted at 18 years of age?

STUDY OBJECTIVE: To determine the frequency of relapse of asthma in young adults in remission at 18 years of age, during a follow-up period of 8 years, and to identify possible prognostic markers for relapse. DESIGN: Longitudinal study of birth cohort (n = 1,037) born in New Zealand in 1972-1973. SETTING: University hospital research clinic. MEASUREMENTS: Participants were assessed at 9, 11, 13, 15, 18, 21, and 26 years of age using a respiratory questionnaire (all ages), spirometry (all ages), bronchodilator response (18 years and 26 years of age), methacholine challenge (9, 11, 13, 15, and 21 years of age), and allergen skin-prick testing (13 years and 21 years of age). RESULTS: Approximately one third of study members (35%) with asthma in remission at 18 years of age relapsed by 21 years or 26 years of age. Atopy and lower FEV(1)/FVC ratio at 18 years of age were significant independent prognostic factors for relapse in multiple logistic regression analyses. Increased responsiveness to methacholine (provocative concentration < 8 mg/mL) or bronchodilator (improvement in FEV(1) >/= 10%) at 21 years of age were more common among those with relapse, but the positive and negative predictive values for a previous positive methacholine challenge test result at 15 years of age were low. Asthma after relapse was generally mild (mean FEV(1) 97.1% predicted). Totally new adult asthma developed by 26 years of age in 9% of study members who had no asthma or wheezing at any time up to 18 years of age. CONCLUSIONS: Subsequent relapse of previously diagnosed asthma in remission at 18 years of age occurs in one in three young adults. Such relapse is not easily predicted, especially by measurements of airway responsiveness. A history of asthma currently in remission should not be used to prejudice employment opportunities for young adults.

Adolescent↗
PubMed2004

Regression methods for covariate adjustment and subgroup analysis for non-censored cost-effectiveness data.

The current interest in undertaking cost-effectiveness analyses alongside clinical trials has lead to the increasing availability of patient-level data on both the costs and effectiveness of intervention. In a recent paper, we show how cost-effectiveness analysis can be undertaken in a regression framework. In the current paper we develop a direct regression approach to cost-effectiveness analysis by proposing the use of a system of seemingly unrelated regression equations to provide a more general method for prognostic factor adjustment with emphasis on sub-group analysis. This more general method can be used in either an incremental cost-effectiveness or an incremental net-benefit approach, and does not require that the set of independent variables for costs and effectiveness be the same. Furthermore, the method can exhibit efficiency gains over unrelated ordinary least squares regression.

Adult↗
PubMed2004

Randomized controlled trial of misoprostol for second-trimester pregnancy termination associated with fetal malformation.

OBJECTIVE: Our purpose was to compare the effectiveness, women's views of the termination procedure, and success of umbilical cord culture for vaginal and oral misoprostol versus intra-amniotic prostaglandin PGF(2alpha) for second-trimester pregnancy termination (STPT). STUDY DESIGN: We randomized 217 women, 15 to 24 weeks' gestation, into 3 groups. Oral (OM) and vaginal (VM) misoprostol groups received 400 microg of misoprostol every 4 hours for 24 hours. The intra-amniotic PGF(2alpha) (IAPG) group received 40 mg of PGF(2alpha) followed by oxytocin infusion. Women completed self-administered questionnaires 3 weeks after the termination procedure. Umbilical cord samples were collected at delivery for karyotype analysis. The primary outcome was the time from start of the procedure to placental delivery. Secondary outcomes were maternal complications, women's acceptance of the termination procedure, and success rates of umbilical cord culture. RESULTS: The time was longer for the OM group (30.5+/-14.4 hours) compared with the VM group (18.3+/-8.2 hours) and the IAPG group (21.1+/-10.2 hours), P<.001 for both comparisons. Women in the VM group reported being more willing to repeat the termination method in the future and reported fewer side effects than those in the other groups, P<.001. Failure rates for umbilical cord cultures were 9.6%, 17.0%, and 45.6% for the VM, OM, and IAPG groups, respectively. CONCLUSION: Oral misoprostol is less effective than intra-amniotic PGF(2alpha) or vaginal misoprostol for STPT. Women report vaginal misoprostol more acceptable than other methods. Umbilical cord culture failure rate is highest in the IAPG group.

Abortifacient Agents, Nonsteroidal↗
PubMed2004

Incremental net benefit in the analysis of economic data from clinical trials, with application to the CADET-Hp trial.

In clinical trials it has become increasingly common for cost data to be collected in addition to data on clinical effectiveness. In response to this, new statistical methodology has been developed. Initially, efforts were focused on the incremental cost-effectiveness ratio, but as the problems with ratio statistics became apparent, attention was switched to incremental net benefit. In this paper statistical methods based on an incremental net benefit approach are given and illustrated with an example from the gastrointestinal literature. The relationship between incremental net benefit and incremental cost-effectiveness is emphasized.

Cost-Benefit Analysis↗