Biomedical subjects

E Goetghebeur

Publications and source records attributed to E Goetghebeur.

5 recordsLinked to original sources

PubMed1999

Practical properties of some structural mean analyses of the effect of compliance in randomized trials.

We can use the structural mean model (SMM) to estimate the mean effect of dose-timing patterns of active treatment actually taken by patients in a randomized placebo-controlled trial. An SMM therefore models the expected difference between a patient's potential response on the treatment arm and potential response on the placebo arm as a function of observed compliance on the treatment arm and baseline predictors. It accounts for the possibly selective nature of noncompliance without needing to model that aspect directly. It nevertheless enjoys the intention-to-treat property of protecting the alpha level when we are testing the hypothesis of no treatment effect. In the presence of selective compliance, classical regression methods lead to inconsistent and seriously biased estimates of the effects of treatment actually taken. The SMM is designed to reduce these problems. This paper studies selectivity and addresses some practical properties of the SMM estimator. Specifically, we use a blood pressure trial to explore the precision of the estimates in practical cases. We also compare mean squared errors (MSEs) of an SMM and the ordinary least-squares (OLS) estimator. We study the effect of baseline covariates on the precision of the SMM estimator and describe the potential role of a run-in period in this regard.

Algorithms↗

PubMed1999

Latent class analysis permits unbiased estimates of the validity of DAT for the diagnosis of visceral leishmaniasis.

BACKGROUND: Substantial uncertainty surrounds the specificity of the Direct Agglutination Test (DAT) for visceral leishmaniasis (VL) in clinical suspects, since no good gold standard exists for unequivocally identifying diseased subjects. We explored the Latent Class Analysis (LCA) modelling technique to circumvent this problem. PATIENTS AND METHODS: Data on 149 clinical suspects recruited in 1993-96 during a multicentre study in Sudan were re-examined. Clinical data, lymph node and bone marrow aspirate and DAT results were available. IFAT was performed in 1997 on stored filter paper blood of 80 individuals. Classical Validity Analysis (CVA) in a 2 x 2 contingency table with parasitology as a gold standard was compared with the parameter estimates produced by the best fitting LCA model. RESULTS: The sensitivity estimates of DAT produced by CVA (98% (89%-100%)) were almost exactly reproduced by LCA. The specificity estimates by LCA were substantially higher than those obtained in CVA. Specificity of DAT depended, however, on whether the subject was treated for VL before. In subjects without prior treatment, CVA estimated DAT specificity at 68% (56%-79%), whereas LCA estimated it at 85% (63%-100%). CONCLUSION: LCA modelling proved a useful tool, as it gave consistent estimates of test characteristics and allowed for control of confounding factors and interaction effects. Since VL is a life-threatening disease for which expensive but effective and safe treatment exists, a clinical suspect in an endemic area should be treated on the basis of a positive DAT result.

Adolescent↗

PubMed1998

Estimating the causal effect of compliance on binary outcome in randomized controlled trials.

We examine likelihood based methods aimed at analysing the causal effect of actual exposure to drug treatment on a (repeated) binary outcome in two randomized trials with partial compliance. Starting with the univariate compliance summary 'total treatment dose history', we apply a method for ordinal compliance and monotone dose response, proposed by Goetghebeur and Molenberghs. In a short duration trial of blood pressure reduction, this summary leads to meaningful effect estimators. However, in the analysis of a vitamin A trial, this method reaches a boundary solution; the estimated possible benefit from vitamin A for children who did not receive any pills on the treatment arm is zero. In our formulation the number of pills that were taken captures part of the outcome, and the corresponding effect parameters suffer from this confounding. To gain additional insight, we account explicitly for the temporal structure of compliance. We extend the likelihood based methodology for univariate ordered compliance to more dimensional compliance with only a partial order structure on exposure. The randomization assumptions in the causal formulation of Rubin are translated to this setting. We motivate a set of parametric assumptions on the joint distribution of potential outcomes and observed compliance levels and reanalyse the vitamin A trial. Our findings suggest that one capsule of vitamin A had a large impact on mortality during the first 4 months. The greatest reduction in risk was estimated amongst children who received two doses. This supports findings from a vitamin A trial in Ghana and in Nepal. Finally, we discuss extensions of this method, covering uncensored and censored grouped survival data.

Adult↗

PubMed1997

Comparing compliance patterns between randomized treatments.

When two equally efficacious drugs enter the market, the one with the better compliance is likely to be more widely used. Special management of the delivery may produce increased compliance. In this paper we analyze a trial of a single drug dosing prescription with patients randomized to either daily self monitoring of the outcome (blood pressure) or not. The study used Medication Event Monitoring Systems (MEMS) to record each exact time and date when a patient opened the pill container. No established method is available for comparing these high-dimensional compliance patterns between groups. This paper investigates several summary measures that highlight different dimensions of the pattern and the drug context in which they may be meaningful. Further, we examine conditional and marginal models that enable comparisons of the full pattern of daily dosing indicators for subjects between the groups. We found no simple difference in average compliance levels, but we found an interesting interaction between treatment and time: similar compliance existed initially among patients in both randomized groups, with a stronger decline over time for patients who did not monitor their blood pressure. We discuss how a balance between simplicity of interpretation and efficiency of data use may be sought in this case.

Antihypertensive Agents↗

PubMed1996

Missing cause of death information in the analysis of survival data.

Goetghebeur and Ryan proposed a method for proportional hazards analyses of competing risks failure-time data when the failure type is missing for some cases. This paper evaluates the properties of the method using data from a clinical trial in Hodgkin's disease. We generated several patterns of missingness in the cause of death in 'pseudo-studies' derived from the study database. We found that the proposed method provided regression coefficients and inferences that were less biased than those from other methods over an increasing percentage of missingness in the failure type when missingness is random, when it depends on an important covariate, when it depends on failure type, and when it depends on follow-up time. We present suggestions for study design with planned missingness in the failure type.

Adult↗