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A R Willan

Publications and source records attributed to A R Willan.

At least 19 recordsLinked to original sources
PubMed2002

Using inverse-weighting in cost-effectiveness analysis with censored data.

Due to induced dependent censoring, estimating mean costs and quality-adjusted survival in a cost-effectiveness analysis using standard life-table methods leads to biased results. In this paper we propose methods for estimating the difference in mean costs and the difference in effectiveness, together with their respective variances and covariance in the presence of dependent censoring. We consider the situation in which the measure of effectiveness is either the probability of patients surviving a duration of interest, mean survival time over a duration of interest or mean quality-adjusted survival time over a duration of interest. The method of inverse-weighting is used for censored cost and quality of life data. The methods are illustrated in an example using an incremental net benefit analysis.

Cost-Benefit Analysis↗
PubMed2001

Cost-effectiveness analysis when the WTA is greater than the WTP.

The incremental cost effectiveness ratio has long been the standard parameter of interest in the assessment of the cost-effectiveness of a new treatment. However, due to concerns with interpretability and statistical inference, authors have suggested using the willingness-to-pay for a unit of health benefit to define the incremental net benefit as an alternative. The incremental net benefit has a more consistent interpretation and is amenable to routine statistical procedures. These procedures rely on the fact that the willingness-to-accept compensation for a loss of a unit of health benefit (at some cost saving) is the same as the willingness-to-pay for it. Theoretical and empirical evidence suggest, however, that in health care the willingness-to-accept is about twice as much as the willingness-to-pay. We use Bayesian methods to provide a statistical procedure for the cost-effectiveness comparison of two arms of a randomized clinical trial that allows the willingness-to-pay and the willingness-to-accept to have different values. An example is provided.

Bayes Theorem↗
PubMed2001

On the probability of cost-effectiveness using data from randomized clinical trials.

BACKGROUND: Acceptability curves have been proposed for quantifying the probability that a treatment under investigation in a clinical trial is cost-effective. Various definitions and estimation methods have been proposed. Loosely speaking, all the definitions, Bayesian or otherwise, relate to the probability that the treatment under consideration is cost-effective as a function of the value placed on a unit of effectiveness. These definitions are, in fact, expressions of the certainty with which the current evidence would lead us to believe that the treatment under consideration is cost-effective, and are dependent on the amount of evidence (i.e. sample size). METHODS: An alternative for quantifying the probability that the treatment under consideration is cost-effective, which is independent of sample size, is proposed. RESULTS: Non-parametric methods are given for point and interval estimation. In addition, these methods provide a non-parametric estimator and confidence interval for the incremental cost-effectiveness ratio. An example is provided. CONCLUSIONS: The proposed parameter for quantifying the probability that a new therapy is cost-effective is superior to the acceptability curve because it is not sample size dependent and because it can be interpreted as the proportion of patients who would benefit if given the new therapy. Non-parametric methods are used to estimate the parameter and its variance, providing the appropriate confidence intervals and test of hypothesis.

Cost-Benefit Analysis↗
PubMed2001

Incremental net benefit in randomized clinical trials.

There are three approaches to health economic evaluation for comparing two therapies. These are (i) cost minimization, in which one assumes or observes no difference in effectiveness, (ii) incremental cost-effectiveness, and (iii) incremental net benefit. The latter can be expressed either in units of effectiveness or costs. When analysing data from a clinical trial, expressing incremental net benefit in units of cost allows the investigator to examine all three approaches in a single graph, complete with the corresponding statistical inferences. Furthermore, if costs and effectiveness are not censored, this can be achieved using common two-sample statistical procedures. The above will be illustrated using two examples, one with censoring and one without.

Amiodarone↗
PubMed2001

Cost prediction models for the comparison of two groups.

For trial-based economic evaluation where patient-specific cost data are not routinely available, cost prediction models are commonly used to estimate total cost for each patient. Typically, multiple regression techniques are used on data from diagnosis-matched, non-trial patients (where patient-level cost data are available) to model cost as a function of covariates that are observed on the trial subjects (e.g. length of hospital stay, procedures, etc.). The estimated beta coefficients provide a means of estimating the total cost for each patient in the trial. However, the variability of the beta coefficients due the measurement and sampling error is seldom included in the overall variance expression for mean costs by treatment group. In this paper we provide a method for estimating this variance and provide an example application

Angina, Unstable↗
PubMed2001

Analysis, sample size, and power for estimating incremental net health benefit from clinical trial data.

Stinnett and Mullahy recently introduced the concept of net health benefit as an alternative to cost-effectiveness ratios for the statistical analysis of patient-level data on the costs and health effects of competing interventions. Net health benefit addresses a number of problems associated with cost-effectiveness ratios by assuming a value for the willingness-to-pay for a unit of effectiveness. We extend the concept of net health benefit to demonstrate that standard statistical procedures can be used for the analysis, power, and sample size determinations of cost-effectiveness data. We also show that by varying the value of the willingness-to-pay, the point estimate and confidence interval for the incremental cost-effectiveness ratio can be determined. An example is provided.

Biometry↗
PubMed2001

Cost effectiveness in Canada of a multidrug prepackaged regimen (Hp-PAC)+ for Helicobacter pylori eradication.

OBJECTIVE: To assess the cost effectiveness of a multidrug prepackaged regimen for Helicobacter pylori, the Hp-PAC (lansoprazole 30mg, clarithromycin 500 mg, amoxicillin 1 g, all twice daily), relative to alternative pharmacological strategies in the management of confirmed duodenal ulcer over a 1-year period from 2 perspectives: (i) a strict healthcare payer perspective (Ontario Ministry of Health) excluding the patient copayment; and (ii) a healthcare payer perspective including the patient copayment. DESIGN: A decision-analytical model was developed to estimate expected per patient costs [1998 Canadian dollars ($ Can)], weeks without ulcer and symptomatic ulcer recurrences for the Hp-PAC compared with: proton pump inhibitor (PPI)-clarithromycin-amoxicillin (PPI-CA), PPI-clarithromycin-metronidazole (PPI-CM), PPI-amoxicillin-metronidazole (PPI-AM) and ranitidine-bismuthmetronidazole-tetracycline (RAN-BMT). MAIN OUTCOME MEASURES AND RESULTS: All PPI-based regimens had higher expected costs but better outcomes relative to RAN-BMT. From a strict healthcare payer perspective, PPI-CM ($Can 209) yielded lower expected costs than PPI-CA ($Can 221) and slightly lower costs than Hp-PAC ($Can 211). However, these 3 regimens all shared identical outcomes (51.2 weeks without ulcer). When the current Ontario, Canada, $Can 2 patient copayment was added to the dispensing fee, Hp-PAC yielded lower costs ($Can 214) than PPI-CM ($Can 216). CONCLUSION: From a strict healthcare payer perspective, Hp-PAC is weakly dominated by PPI-CM with an incremental cost effectiveness (relative to RAN-BMT) of $Can 5.77 per ulcer week averted. When the patient copayment is added to this perspective, Hp-PAC weakly dominates PPI-CM ($Can 5 per ulcer week averted). Regardless of perspective, Hp-PAC and PPI-CM differed by only $Can 2 per patient over 1 year and the expected time without ulcer was 51.2 weeks for both. More data on the clinical and statistical differences in H. pylori eradication with Hp-PAC and PPI-CM would be useful. This analysis does not in clude the possible advantage of Hp-PAC in terms of compliance and antibacterial resistance.

Anti-Bacterial Agents↗
PubMed2000

Planned caesarean section versus planned vaginal birth for breech presentation at term: a randomised multicentre trial. Term Breech Trial Collaborative Group.

BACKGROUND: For 3-4% of pregnancies, the fetus will be in the breech presentation at term. For most of these women, the approach to delivery is controversial. We did a randomised trial to compare a policy of planned caesarean section with a policy of planned vaginal birth for selected breech-presentation pregnancies. METHODS: At 121 centres in 26 countries, 2088 women with a singleton fetus in a frank or complete breech presentation were randomly assigned planned caesarean section or planned vaginal birth. Women having a vaginal breech delivery had an experienced clinician at the birth. Mothers and infants were followed-up to 6 weeks post partum. The primary outcomes were perinatal mortality, neonatal mortality, or serious neonatal morbidity; and maternal mortality or serious maternal morbidity. Analysis was by intention to treat. FINDINGS: Data were received for 2083 women. Of the 1041 women assigned planned caesarean section, 941 (90.4%) were delivered by caesarean section. Of the 1042 women assigned planned vaginal birth, 591 (56.7%) delivered vaginally. Perinatal mortality, neonatal mortality, or serious neonatal morbidity was significantly lower for the planned caesarean section group than for the planned vaginal birth group (17 of 1039 [1.6%] vs 52 of 1039 [5.0%]; relative risk 0.33 [95% CI 0.19-0.56]; p<0.0001). There were no differences between groups in terms of maternal mortality or serious maternal morbidity (41 of 1041 [3.9%] vs 33 of 1042 [3.2%]; 1.24 [0.79-1.95]; p=0.35). INTERPRETATION: Planned caesarean section is better than planned vaginal birth for the term fetus in the breech presentation; serious maternal complications are similar between the groups.

Adult↗
PubMed2000

Cancer care workers in Ontario: prevalence of burnout, job stress and job satisfaction.

BACKGROUND: Cancer Care Ontario's Systemic Therapy Task Force recently reviewed the medical oncology system in the province. There has been growing concern about anecdotal reports of burnout, high levels of stress and staff leaving or decreasing their work hours. However, no research has systematically determined whether there is evidence to support or refute these reports. To this end, a confidential survey was undertaken. METHODS: A questionnaire was mailed to all 1016 personnel of the major providers of medical oncology services in Ontario. The questionnaire consisted of the Maslach Burnout Inventory, the 12-item General Health Questionnaire, a questionnaire to determine job satisfaction and stress, and questions to obtain demographic characteristics and to measure the staff's consideration of alternative work situations. RESULTS: The overall response rate was 70.9% (681 of 961 eligible subjects): by group it was 63.3% (131/207) for physicians, 80.9% (314/388) for allied health professionals and 64.5% (236/366) for support staff. The prevalence of emotional exhaustion were significantly higher among the physicians (53.3%) than among the allied health professionals (37.1%) and the support staff (30.5%) (p < or = 0.003); the same was true for feelings of depersonalization (22.1% v. 4.3% and 5.5% respectively) (p < or = 0.003). Feelings of low personal accomplishment were significantly higher among physicians (48.4%) and allied health professionals (54.0%) than among support staff (31.4%) (p < or = 0.002). About one-third of the respondents in each group reported that they have considered leaving for a job outside the cancer care system. Significantly more physicians (42.6%) than allied health professionals (7.6%) or support staff (4.5%) stated that they have considered leaving for a job outside the province. INTERPRETATION: The findings support the concern that medical oncology personnel are experiencing burnout and high levels of stress and that large numbers are considering leaving or decreasing their work hours. This is an important finding for the cancer care system, where highly trained and experienced health care workers are already in short supply.

Burnout, Professional↗
PubMed2000

Treatment outcomes for squamous intraepithelial lesions.

OBJECTIVE: To assess the effectiveness of cone biopsy, cryotherapy, laser ablation and the loop electrosurgical procedure in the treatment of squamous intraepithelial lesions. METHOD: Systematic review of randomized controlled trials in subjects who underwent treatment of low- and high-grade squamous intraepithelial lesions with these modalities. Main outcome measures included the following: percent resolution and persistence of a lesion and notable complications for each procedure. RESULT: Pooled rates of resolution for low-grade, high-grade, or combined squamous intraepithelial lesions were similar across the different treatment modalities (range 85.2-94.7%), with substantial overlap among the 95% confidence intervals. Significant hemorrhage occurred most frequently in subjects who received cone biopsy (4.6%) (95% CI: 2.15, 6.99), followed by laser ablation (1.75%) (95% CI: 0.70, 2.81), and LEEP (1.35%) (95% CI: 0.24, 2.47). No hemorrhages were reported among subjects who received cryotherapy. Study sample sizes were relatively small. There were no reported cases of progression to invasive cancer, but duration of follow-up (median follow-up time for all eligible studies = 12 months) was not sufficient to evaluate long-term outcomes. CONCLUSIONS: There were no substantive differences in outcomes regarding persistence and resolution in the treatment of squamous intraepithelial lesions for subjects receiving cone biopsy, cryotherapy, laser ablation, or LEEP.

Biopsy↗
PubMed2000

A phase I study of oxidized raffinose cross-linked human hemoglobin.

OBJECTIVE: To evaluate the safety of oxidized-raffinose cross-linked human hemoglobin, Hemolink, in normal healthy volunteers. DESIGN: Randomized, placebo-controlled, double-blind study. SETTING: Clinical research facility of a contract research organization. PATIENTS: Forty-two healthy adult male volunteers of which 33 received Hemolink. INTERVENTIONS: Oxidized-raffinose cross-linked and polymerized hemoglobin as a 10% (w/v) solution, in doses of 0.025-0.6 g/kg or an equivalent volume of lactated Ringer's solution, was infused intravenously on day 1, and subjects were monitored for 3 days in the clinical facility with < or =6 wks follow-up. Major organ function was assessed pre- and postinfusion, by hemodynamic, electrocardiographic, pulmonary function, and clinical chemistry measurements. MEASUREMENTS AND MAIN RESULTS: Doses of 1.7-42 g of hemoglobin were administered with no serious adverse events noted. Abdominal pain of moderate to severe intensity was seen in some subjects at doses >0.4 g/kg and was alleviated with smooth muscle relaxants. There was a dose-dependent increase in mean arterial pressure with a plateau of approximately 14% above baseline at 0.1 g/kg. There was a concomitant reduction in heart rate, with no electrocardiographic abnormalities found. Respiratory function was not affected. There was a dose-dependent increase in serum bilirubin with values above the upper limit of normal at doses of > or =0.4 g/kg. Small increases in aspartate aminotransferase and alanine aminotransferase were noted in some patients, whereas alkaline phosphatase and gamma-glutamyltransferase remained in the normal range. Serum amylase concentrations were normal in 31 of 33 patients receiving Hemolink, whereas lipase was within the normal range in 21 of 33 patients. LDH was increased in a dose-dependent fashion. Two patients had increased creatine kinase concentrations, with a normal creatine kinase-MB mass fraction. All hematologic variables were within the normal range. The half-life of the oligomeric (>64 kDa) fraction of Hemolink was 18-20 hrs. CONCLUSION: Oxidized-raffinose cross-linked hemoglobin, Hemolink, at doses < or =0.6 g/kg were well tolerated in healthy volunteers with no evidence of organ dysfunction. Further investigation of its potential use in surgical and trauma settings appears warranted.

Adult↗
PubMed2000

Quality of life in spina bifida: importance of parental hope.

BACKGROUND AND AIMS: Prognosis in spina bifida (SB) is often based only on neurological deficits present at birth. We hypothesised that both parental hope and the neurophysical examination predict quality of life in children and adolescents with SB. METHODS: A previously validated disease and age specific health related quality of life (HRQL) instrument was posted to families of children (aged 5-12 years) and adolescents (aged 13-20 years) with SB. We measured parental hope, determined the child's current physical function, and obtained retrospective data on the neonatal neurophysical examination (NPE). Regression analysis modelled HRQL firstly as a dependent variable on parental hope and NPE ("birth status"); and secondly on parental hope and current physical function ("current function"). RESULTS: Response rates were 71% (137 of 194) for families of children, and 54% (74 of 138) for families of adolescents. NPE data were available for 121 children and 60 adolescents. In children, the birth status model predicted 26% of the variability (R(2) hope 21%) compared with 23% of the variability (R(2) hope 23%)in the adolescents. The current function model explained 47% of the variability (R(2) hope 19%) in children compared with 31% of the variability (R(2) hope 24%) in the adolescents. CONCLUSIONS: In both age groups, parental hope was more strongly associated with the HRQL than neonatal or current physical deficits. A prospective study is required to determine whether a causal relation exists between parental hope and HRQL of children and adolescents with SB.

Adolescent↗
PubMed2000

Comparison of two standardized methods of methacholine inhalation challenge in young adults.

In the European Community Respiratory Health Study (ECRHS), airway responsiveness to methacholine was determined using the Mefar dosimeter protocol. Elsewhere, the 2-min tidal breathing method has become the preferred standardized method. The relationship between measurements of responsiveness by these two methods is not well established. This study measured airway responsiveness to methacholine by dosimeter and tidal breathing methods in 47 healthy asthmatic subjects aged 20-44 yrs. Tests were performed within 1 week and in random order. Baseline forced expiratory volume in one second (FEV1) varied by <10% between tests in 42/47 subjects. There was a close association between responsiveness determined by the two methods. A provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) value of < or =8.0 mg x mL(-1) (tidal method) used to categorize airway hyperresponsiveness agreed most closely with a provocative dose of methacholine causing a 20% fall in FEV1 (PD20) value of < or =0.5 mg (dosimeter method) (kappa statistic 0.78). Each doubling or halving of PC20 to define a level of hyperresponsiveness agreed closely with a doubling or halving of PD20. Assessment of airway responsiveness as provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second by the Mefar dosimeter protocol gave a close and predictable relationship with provocative concentration of methacholine causing a 20% fall in expiratory volume in one second assessed using the tidal breathing method. Airway hyperresponsiveness as determined by the accepted criterion of provocative concentration of methacholine causing a 20% fall in expiratory volume in one second < or =8 mg x mL(-1) was best correlated with provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second <0.5 mg by Mefar dosimeter.

Administration, Inhalation↗
PubMed1999

Sample size and power issues in estimating incremental cost-effectiveness ratios from clinical trials data.

It is becoming increasingly more common for a randomized controlled trial of a new therapy to include a prospective economic evaluation. The advantage of such trial-based cost-effectiveness is that conventional principles of statistical inference can be used to quantify uncertainty in the estimate of the incremental cost-effectiveness ratio (ICER). Numerous articles in the recent literature have outlined and compared various approaches for determining confidence intervals for the ICER. In this paper we address the issue of power and sample size in trial-based cost-effectiveness analysis. Our approach is to determine the required sample size to ensure that the resulting confidence interval is narrow enough to distinguish between two regions in the cost-effectiveness plane: one in which the new therapy is considered to be cost-effective and one in which it is not. As a result, for a given sample size, the cost-effectiveness plane is divided into two regions, separated by an ellipse centred at the origin, such that the sample size is adequate only if the truth lies on or outside the ellipse.

Antineoplastic Agents↗
PubMed1999

Predictors of cesarean delivery after prelabor rupture of membranes at term.

OBJECTIVE: To identify the significant predictors of cesarean delivery after prelabor rupture of membranes (PROM) at term. METHODS: In a multicenter study involving 72 institutions in six countries, 5041 women were randomized to induction of labor with oxytocin or prostaglandins or to expectant management. We did univariate and multivariate logistic regression analyses to determine the statistically significant independent predictors of cesarean delivery (P < .05). RESULTS: The following variables were found to be significantly associated with cesarean delivery: delivery in Israel, versus Canada (odds ratio [OR] 0.34); delivery in Australia, versus Canada (OR 1.93); nulliparity (OR 2.81); labor lasting more than 12 hours, versus less than 6 hours (OR 2.78); labor lasting 6-12 hours, versus less than 6 hours (OR 1.66); previous cesarean delivery (OR 2.75); epidural anesthesia (OR 2.66); clinical chorioamnionitis (OR 2.42); internal fetal heart rate monitoring (OR 2.19); birth weight of at least 4000 g (OR 2.07); use of oxytocin (OR 1.97); maternal age of at least 35 years (OR 1.44); latent period of at least 12 hours (OR 1.41); and meconium staining (OR 1.41). CONCLUSION: Strong predictors of cesarean delivery after PROM at term were country of birth, nulliparity, long labor, previous cesarean delivery, and epidural anesthesia.

Adult↗
PubMed1998

Natural history of cervical squamous intraepithelial lesions: a meta-analysis.

OBJECTIVE: To define the strengths and weaknesses of existing research on the natural history of cervical squamous intraepithelial lesions (SIL) and to estimate rates of progression and regression without treatment. DATA SOURCES: Studies of women whose cervical smears showed squamous atypia or worse and who were observed for a minimum of 6 months were identified by a search of MEDLINE from 1966 to 1996, Current Contents, the Federal Research in Progress database, and references of review articles and identified studies, and by experts in the field. METHODS OF STUDY SELECTION: Fifteen of 81 studies were eligible for data extraction. To be eligible, studies had to report a minimum of 6 months' follow-up without treatment; relate entry cytologic findings to outcomes; and report entry cytologic findings so that the study population could be stratified into categories of atypical cells of undetermined significance (ASCUS), low-grade SIL, or high-grade SIL. Studies published before 1970 were excluded. TABULATION, INTEGRATION, AND RESULTS: Eligible studies, representing 27,929 patients, were stratified according to entry cytologic findings. The following rates of progression to high-grade SIL at 24 months were found: ASCUS, 7.13% (95% confidence interval [CI] 0.8%, 13.5%); low-grade SIL, 20.81% (6.08%, 35.55%); and high-grade SIL, 23.37% (12.82%, 32.92%). The following rates of invasive cancer at 24 months were found: ASCUS, 0.25% (0%, 2.25%); low-grade SIL, 0.15% (0%, 0.71%); and high-grade SIL, 1.44% (0%, 3.95%). The following rates of regression to normal were found: ASCUS, 68.19% (57.51%, 78.86%); low-grade SIL, 47.39% (35.92%, 58.86%); and high-grade SIL, 35.03% (16.57%, 53.49%). Study heterogeneity was not explained by regression analysis of study level variables. CONCLUSION: Our findings for borderline and low-grade abnormal cervical cytologic results suggest a relatively low risk of invasive cervical cancer with observation up to 24 months and support the clinical policy of early colposcopy for high-grade lesions.

Carcinoma in Situ↗
PubMed1998

Economic evaluation of chemotherapy with mitoxantrone plus prednisone for symptomatic hormone-resistant prostate cancer: based on a Canadian randomized trial with palliative end points.

PURPOSE: To evaluate the economic consequences of the use of chemotherapy in patients with symptomatic hormone-resistant prostate cancer (HRPC) in the context of a previously published Canadian open-label, phase III, randomized trial with palliative end points. PATIENTS AND METHODS: The trial randomized 161 patients to initial treatment with mitoxantrone and prednisone (M + P) or to prednisone alone (P) and showed better palliation with M + P. There was no significant difference in survival. A detailed retrospective chart review was performed of resources used from randomization until death of 114 of 161 patients enrolled at the three largest centers: these included hospital admissions, outpatient visits, investigations, therapies (which included all chemotherapy and radiation), and palliative care. Cancer center and community hospital costs were calculated by using the hotel approximation method and case costing from the Ontario Case Cost Project, respectively. Cost-utility analysis was performed by transforming the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 global quality-of-life item measured every 3 weeks on trial to an estimate of utility, and extending the last known value through to death or last follow-up. RESULTS: The mean total cost until death or last follow-up by intention-to-treat was M + P CDN $27,300; P CDN $29,000. The 95% confidence intervals on the observed cost difference ranged from a saving of $9,200 for M + P (with palliative benefit) to an increased cost of $5,800 for M + P. The major proportion of cost (M + P 53% v P 66%; CDN $14,500 v $19,100) was for inpatient care. Initial M + P was consistently less expensive in whichever time period was used to compare costs. Cost-utility analysis showed M + P to be the preferred strategy with an upper 95% confidence interval for the incremental cost-utility ratio of CDN $19,700 per quality-adjusted life-year (QALY). CONCLUSION: A treatment that reduces symptoms and improves quality of life has the potential to reduce costs in other areas. Economic factors should not influence the clinical decision as to whether to use M + P in a symptomatic patient.

Canada↗