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E Lesaffre

Publications and source records attributed to E Lesaffre.

At least 37 records · Page 2Linked to original sources
PubMed2000

Fraud in medical research: an international survey of biostatisticians. ISCB Subcommittee on Fraud.

The characteristics of scientific fraud and its impact on medical research are in general not well known. However, the interest in the phenomenon has increased steadily during the last decade. Biostatisticians routinely work closely with physicians and scientists in many branches of medical research and have therefore unique insight into data. In addition, they have methodological competence to detect fraud and could be expected to have a professional interest in valid results. Biostatisticians therefore are likely to provide reliable information on the characteristics of fraud in medical research. The objective of this survey of biostatisticians, who were members of the International Society for Clinical Biostatistics, was to assess the characteristics of fraud in medical research. The survey was performed between April and July 1998. The participation rate was only 37%. We report the results because a majority (51%) of the participants knew about fraudulent projects, and many did not know whether the organization they work for has a formal system for handling suspected fraud or not. Different forms of fraud (e.g., fabrication and falsification of data, deceptive reporting of results, suppression of data, and deceptive design or analysis) had been observed in fairly similar numbers. We conclude that fraud is not a negligible phenomenon in medical research, and that increased awareness of the forms in which it is expressed seems appropriate. Further research, however, is needed to assess the prevalence of different types of fraud, as well as its impact on the validity of results published in the medical literature.

Biometry↗
PubMed2000

Estimating the power of compliance-improving methods.

Measuring patient compliance with prescribed or protocol-specified regimens of drug administration is an important topic in clinical trial research. One of the most useful expressions of compliance is the proportion of days the prescribed dose was taken correctly, but the distribution of this variable is often bimodal. We show that a two-component mixture of beta distributions can be fitted to these data. The two components can be interpreted as the groups of poorly and satisfactorily complying patients, respectively. This representation was helpful in the calculation of the power in a recent trial of a method to improve the compliance of patients with a lipid-lowering drug regimen. Control Clin Trials 2000;21:540-551

Bias↗
PubMed2000

The value of the number-needed-to-treat method in antiepileptic drug trials.

PURPOSE: There is controversy between clinicians and statisticians on the appropriateness of the number needed to treat (NNT) as a summary statistic to report the effectiveness of a treatment. We examine the two viewpoints and make proposals concerning the reporting of clinical trial results. METHODS: In the context of antiepileptic treatments, we explain the two different viewpoints and illustrate the use of the odds ratio, relative risk, absolute difference, and NNT on the results of randomized clinical trials with topiramate (TPM). Special attention is paid to the use of these summary statistics in meta-analyses. Here, the NNT is the expected number of patients one would need to treat to achieve a single occurrence of a specified good outcome (e.g., 50% reduction in seizure rate) in comparison to no (or placebo) treatment. RESULTS: Although the NNT is readily interpretable in some instances, it exhibits undesirable statistical behavior in other cases. In particular, confidence intervals for the NNT may split into two intervals and extend to positive and negative infinity when treatment efficacy is not clearly established by the data. Meta-analyses cannot be sensibly conducted directly on the NNT scale. CONCLUSIONS: Although other measures, such as the odds ratio, have been more commonly used in the context of meta-analyses, clinicians prefer the NNT because it gives them a clearer clinical interpretation of the effectiveness of a (new) treatment. On the other hand, statisticians do not recognize the value of the NNT, as it has undesirable statistical properties. Some reconciliation between the two views could be achieved when the clinicians acknowledge the weak aspects of the NNT and when statisticians realize that statistical appropriateness is not the same as clinical relevance. It is suggested that the NNT be used as a secondary reporting tool not on an equal footing with the classic scales.

Anticonvulsants↗
PubMed2000

An overview of group sequential methods in longitudinal clinical trials.

During the last decade, several papers have been published on group sequential methods in general and on sequential longitudinal clinical trials in particular. This paper gives an overview of the proposed methods, emphasizing longitudinal clinical trials. Furthermore, it tries to answer some practical questions that may arise during the conduct of interim analyses in longitudinal trials. Simulations have been carried out to obtain insight in these practical considerations.

Clinical Trials as Topic↗
PubMed1999

The role of biostatistics in the prevention, detection and treatment of fraud in clinical trials.

Recent cases of fraud in clinical trials have attracted considerable media attention, but relatively little reaction from the biostatistical community. In this paper we argue that biostatisticians should be involved in preventing fraud (as well as unintentional errors), detecting it, and quantifying its impact on the outcome of clinical trials. We use the term 'fraud' specifically to refer to data fabrication (making up data values) and falsification (changing data values). Reported cases of such fraud involve cheating on inclusion criteria so that ineligible patients can enter the trial, and fabricating data so that no requested data are missing. Such types of fraud are partially preventable through a simplification of the eligibility criteria and through a reduction in the amount of data requested. These two measures are feasible and desirable in a surprisingly large number of clinical trials, and neither of them in any way jeopardizes the validity of the trial results. With regards to detection of fraud, a brute force approach has traditionally been used, whereby the participating centres undergo extensive monitoring involving up to 100 per cent verification of their case records. The cost-effectiveness of this approach seems highly debatable, since one could implement quality control through random sampling schemes, as is done in fields other than clinical medicine. Moreover, there are statistical techniques available (but insufficiently used) to detect 'strange' patterns in the data including, but no limited to, techniques for studying outliers, inliers, overdispersion, underdispersion and correlations or lack thereof. These techniques all rest upon the premise that it is quite difficult to invent plausible data, particularly highly dimensional multivariate data. The multicentric nature of clinical trials also offers an opportunity to check the plausibility of the data submitted by one centre by comparing them with the data from all other centres. Finally, with fraud detected, it is essential to quantify its likely impact upon the outcome of the clinical trial. Many instances of fraud in clinical trials, although morally reprehensible, have a negligible impact on the trial's scientific conclusions.

Biometry↗
PubMed1999

Assessing the goodness-of-fit of the Laird and Ware model--an example: the Jimma Infant Survival Differential Longitudinal Study.

The Jimma Infant Survival Differential Longitudinal Study is an Ethiopian study, set up to establish risk factors affecting infant survival and to investigate socio-economic, maternal and infant-rearing factors that contribute most to the child's early survival. Here, a subgroup of about 1500 children born in Jimma town is examined for their first year's weight gain. Of special interest is the impact of certain cultural practices like uvulectomy, milk teeth extraction and butter swallowing, on child's weight gain; these have never been thoroughly investigated in any study. In this context, the linear mixed model (Laird and Ware) is employed. The purpose of this paper is to illustrate the practical issues when constructing the longitudinal model. Recently developed diagnostics will be used herefor. Finally, special attention will be paid to the two-stage interpretation of the linear mixed model.

Adult↗
PubMed1999

A note on the number needed to treat.

The concept of the average number of patients needed to treat to prevent a single bad outcome is becoming increasingly popular among clinicians. Defined as the inverse of the absolute risk reduction (delta), its sample estimate is denoted as NNT. Here we discuss the mathematical and statistical properties of NNT and show that simple calculations, like taking sums of different NNTs, can give nonsensical results. The implication for a meta-analysis expressed in NNTs is that we can best calculate the combined NNT by taking the inverse of the combined estimate for delta. Simulations illustrate the better performance of the combined NNT estimate on the delta-scale (NNT(P)) in comparison with the combined estimate of NNT on the NNT-scale (NNT(O)), even in cases where it is reasonable to take sums. The calculations are illustrated using data from anti-epileptic trials.

Anticonvulsants↗
PubMed1999

Consequences of MRSA carriage in nursing home residents.

A prospective cohort study with 1 year follow-up evaluated the relation between MRSA carriage and mortality, likelihood of hospitalization and functional status in residents of a nursing home for the elderly. Included were all 447 residents living in the home in early June 1994. From all patients, swabs were taken from nose, throat and perineum. Additional swabs (sputum, urine or wounds) were taken when indicated. The relative risk (RR) of dying within 6 months in MRSA carriers compared to non-carriers was 2.29 (95% CI = 1.04-5.04). This RR remained stable (1.57-2.40) after adjustment for co-variables using Mantel-Haenszel stratified analysis. After I year, the RR was reduced to 1.30 (95% CI = 0.65-2.58). Univariate survival analysis confirmed a difference in survival between carriers and non-carriers after 6 months (log-rank P = 0.04) and no difference after 1 year. Cox regression analysis resulted in a hazard ratio for dying within 6 months of 1.73 (95% CI = 0.72-4.17). No relation was found between carriage and either likelihood of hospitalization or indicators of functional status. These results are compatible with a possible relation between 6 months mortality and MRSA carriage in nursing home patients. It calls for a large scale, multicentre cohort study in order to either confirm or refute these findings.

Aged↗
PubMed1999

Plantar force distribution in Parkinsonian gait: a comparison between patients and age-matched control subjects.

This study aimed to ascertain whether roll-off of the feet during gait was essentially different in patients with Parkinson's disease from that of elderly control subjects. Twenty-two patients, belonging mainly to Hoehn & Yahr grades III and IV, and 30 elderly people participated in the study. Plantar force distribution data were collected of two consecutive strides using pressure-sensitive insoles as part of the pododynograph system. Results showed that when correcting for gait speed and sex differences, patients with Parkinson's disease walked with significantly lower relative peak forces at the forefoot and heel and increased load at the midfoot. The onset of peak forces indicated slower load acceptance on the heel and early forefoot loading which was confirmed by a reduced amplitude of the centre of force along the length of the foot compared with healthy controls. Roll-off was significantly reduced in patients with Parkinson, a feature which was specific for the disease rather than a result of reduced gait speed alone.

Aged↗
PubMed1999

Hemorrhagic transformation within 36 hours of a cerebral infarct: relationships with early clinical deterioration and 3-month outcome in the European Cooperative Acute Stroke Study I (ECASS I) cohort.

BACKGROUND AND PURPOSE: The clinical correlates of the varying degrees of early hemorrhagic transformation of a cerebral infarct are unclear. We investigated the cohort of a randomized trial of thrombolysis to assess the early and late clinical course associated with different subtypes of hemorrhagic infarction (HI) and parenchymal hematoma (PH) detected within the first 36 hours of an ischemic stroke. METHODS: We exploited the database of the European Cooperative Acute Stroke Study I (ECASS I), a randomized, placebo-controlled, phase III trial of intravenous recombinant tissue plasminogen activator in acute ischemic stroke. Findings on 24- to 36- hour CT were classified into 5 categories: no hemorrhagic transformation, HI types 1 and 2, and PH types 1 and 2. We assessed the risk of concomitant neurological deterioration and of 3-month death and disability associated with subtypes of hemorrhagic transformation, as opposed to no bleeding. Risks were adjusted for age and extent of ischemic damage on baseline CT. RESULTS: Compared with absence of hemorrhagic transformation, HI1, HI2, and PH1 did not modify the risk of early neurological deterioration, death, and disability, whereas, in both the placebo and the recombinant tissue plasminogen activator groups, PH2 had a devastating impact on early neurological course (odds ratio for deterioration, 32.3; 95% CI, 13. 4 to 77.7), and on 3-month death (odds ratio, 18.0; 95% CI, 8.05 to 40.1). Risk of disability was also higher, but not significantly, after PH2. CONCLUSIONS: Risk of early neurological deterioration and of 3-month death was severely increased after PH2, indicating that large hematoma is the only type of hemorrhagic transformation that may alter the clinical course of ischemic stroke.

Age Factors↗
PubMed1999

Neurological deterioration in acute ischemic stroke: potential predictors and associated factors in the European cooperative acute stroke study (ECASS) I.

BACKGROUND AND PURPOSE: The present study was undertaken to identify potential predictors of and factors associated with early and late progression in acute stroke. We performed secondary analysis of the clinical, biochemical, and radiological data recorded in the acute phase of stroke patients enrolled in the European Cooperative Acute Stroke Study (ECASS) I. METHODS: Early progressing stroke (EPS) was diagnosed when there was a decrease of > or = 2 points in consciousness or motor power or a decrease of > or = 3 points in speech scores in the Scandinavian Neurological Stroke Scale from baseline to the 24-hour evaluation, and late progressing stroke (LPS) was diagnosed when 1 of these decreases occurred between the 24-hour evaluation and the evaluation at day 7. Using logistic regression analyses, we looked for baseline variables that predicted EPS and LPS and for factors measured after the early or late acute phase and associated with the 2 clinical courses. RESULTS: Of the 615 patients studied, 231 (37.5%) worsened during the first 24 hours after inclusion. The overall incidence of EPS was 37% in the placebo group and 38% in the recombinant tissue plasminogen activator group (P=0.68, Fisher's Exact Test). Focal hypodensity (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.3 to 2.9) and hyperdensity of the middle cerebral artery sign (OR, 1.8; 95% CI, 1.1 to 3.1) on baseline computed tomography, longer delay until treatment (OR, 1.2; 95% CI, 1.1 to 1. 4) and history of coronary heart disease (OR, 1.7; 95% CI, 1.1 to 2. 8) and diabetes (OR, 1.8; 95% CI, 1.0 to 3.1) were independent prognostic factors for EPS. Extent of hypodensity >33% in the middle cerebral artery territory (OR, 2.5; 95% CI, 1.6 to 4.0) and brain swelling (OR, 1.8; 95% CI, 1.1 to 3.2) on CT at 24 hours but not hemorrhagic transformation of cerebral infarct nor decrease in systolic blood pressure within the first 24 hours after treatment were associated with EPS in multivariate analyses. LPS was observed in 20.3% of patients. Older age, a low neurological score, and brain swelling at admission independently predicted late worsening. CONCLUSION: In the setting of a multicenter trial, EPS and LPS are mainly related to computed tomographic signs of cerebral edema. Treatment with recombinant tissue plasminogen activator, hemorrhagic transformation, and moderate changes in systolic blood pressure did not influence the early clinical course.

Aged↗
PubMed1999

Association of hyperdense middle cerebral artery sign with clinical outcome in patients treated with tissue plasminogen activator.

BACKGROUND AND PURPOSE: The hyperdense middle cerebral artery sign (HMCAS) is a marker of thrombus in the middle cerebral artery. The aim of our study was to find out the frequency of the HMCAS, its association with initial neurological severity and early parenchymal ischemic changes on CT, its relevance to clinical outcome, and the efficacy of intravenous recombinant tissue plasminogen activator (rtPA) in patients with the HMCAS. METHODS: Secondary analysis of the data from 620 patients who received either rtPA or placebo in the European Cooperative Acute Stroke Study I (ECASS I), a double-blind, randomized, multicenter trial. The baseline CT scans were obtained within 6 hours from the onset of symptoms. Functional and neurological outcomes were assessed using the modified Rankin Scale and the Scandinavian Stroke Scale at day 90. RESULTS: We found an HMCAS in 107 patients(17.7%). The initial neurological deficit was more severe in patients with the HMCAS than in those lacking this sign (P<0.0001). Early cerebral edema and mass effect were also more common in patients with the HMCAS (P<0.0001). The HMCAS was related to the risk of poor functional outcome (grade of 3 to 6 on the modified Rankin Scale) on univariate analysis: 90 patients (84%) with the HMCAS and 310 patients (62%) lacking this sign were dependent or dead at day 90 (P<0.0001). However, this association was no longer significant in a logistic model accounting for the effect of age, sex, treatment with rtPA, initial severity of neurological deficit and early parenchymal ischemic changes on CT. Patients with the HMCAS who were given rtPA had better neurological recovery than those who received placebo (P=0.0297). CONCLUSIONS: The HMCAS is associated with severe brain ischemia and poor functional outcome. However, it has no significant independent prognostic value when accounting for the effect of initial severity of neurological deficit and of early parenchymal ischemic changes on CT. Patients with the HMCAS may benefit from intravenous rtPA.

Acute Disease↗
PubMed1998

The detection of residual serial correlation in linear mixed models.

Diggle (1988) described how the empirical semi-variogram of ordinary least squares residuals can be used to suggest an appropriate serial correlation structure in stationary linear mixed models. In this paper, this approach is extended to non-stationary models which include random effects other than intercepts, and will be applied to prostate cancer data, taken from the Baltimore Longitudinal Study of Aging. A simulation study demonstrates the effectiveness of this extended variogram for improving the covariance structure of the linear mixed model used to describe the prostate data.

Analysis of Variance↗
PubMed1998

Variceal pressure is a factor predicting the risk of a first variceal bleeding: a prospective cohort study in cirrhotic patients.

Predictive criteria for a first variceal hemorrhage lack substantial accuracy. Cross-sectional studies suggest a close relationship between variceal pressure (VP) and the occurrence of variceal bleeding. In the present prospective cohort study, the significance of VP measurement for prediction of a first variceal bleed was assessed. Eighty-seven patients with cirrhosis and large esophageal varices who had never developed variceal bleeding were followed for 12 months. The endpoint of the study was the presentation or not of a variceal hemorrhage. Thirty-four patients (39%) were in Child's class A, 37 in class B (43%), and 16 in class C (18%). The median interval between endoscopic diagnosis of varices and the beginning of the study was 15 months. Twenty-eight patients (32%) developed a variceal hemorrhage with a bleeding-related mortality of 18% (n=5). The 1-year mortality overall was 16% (n=14). Variables predictive of a first bleed identified by Cox proportional hazards regression model were: the level of VP, the North Italian Endoscopic Club (NIEC) score, and the interval between the diagnosis of varices and the start of the study. By adding VP to NIEC, a significant gain in prognostic accuracy was obtained (P = .003). In conclusion, the present study provides evidence that the level of VP is a major predictive factor for variceal hemorrhage, and that it provides further prognostic information in addition to the NIEC index.

Adult↗
PubMed1998

Twelve weeks of continuous oral therapy for toenail onychomycosis caused by dermatophytes: a double-blind comparative trial of terbinafine 250 mg/day versus itraconazole 200 mg/day.

BACKGROUND: Dermatophyte infections of the toenail have been difficult to treat, requiring long courses of therapy and having high recurrence rates. New oral antifungal agents with better outcomes and minimal adverse events are needed. OBJECTIVE: The purpose of this study was to compare two newer antifungal compounds, terbinafine and itraconazole, for efficacy and safety in toenail onychomycosis caused by dermatophytes. METHODS: The study was randomized and double-blind. It compared 12 weeks of continuous oral treatment with terbinafine 250 mg/day or itraconazole 200 mg/day for confirmed toenail dermatophyte onychomycosis. Clinical symptoms and mycologic outcome were assessed at weeks 4, 8, 12, 24, 36, and 48. A total of 372 patients (186 in each group) with dermatophyte infection confirmed by microscopy and culture were included in the intent-to-treat analysis. RESULTS: At week 48, a statistically significantly greater percentage of the terbinafine group than itraconazole group showed negative mycology (73% [119 of 163] vs 45.8% [77 of 168]; p < 0.0001) (difference = 27.2%; 95% CI = [17.0%, 37.3%]). The difference was also confirmed clinically (p = 0.001) in the patients who were clinically cured or had only minimal symptoms at the end of the study (76.2% [125 of 164] vs 58.1% [100 of 172]) (difference = 18.1%; 95% CI = [8.24%, 27.9%]). The geometric mean length of healthy nail of the big toe was significantly greater in the terbinafine than itraconazole group (8.1 vs 6.4 mm; p = 0.026). Tolerability was good to very good in almost 90% of patients in both groups, and all reported adverse events were known for these compounds. CONCLUSION: Terbinafine produced higher rates of clinical and mycologic cure at follow-up than did itraconazole.

Administration, Oral↗
PubMed1998

A frequency and correlation analysis of motor deficits in Parkinson patients.

PURPOSE: The present study explored the frequency and pattern of functional motor problems of a group of Parkinson patients, as a first step towards developing a rational approach to rehabilitation intervention addressing the primary symptoms of the disease. METHOD: Sixty patients, consisting of 40% women and 60% men with a mean age of 63.5 years and of which 88% were taking L-dopa, underwent a number of standardized clinical tests including part III of the UPDRS. They were also interviewed about the frequency of motor problems occurring at home. RESULTS: Loss of trunk rotation as expressed in rolling in supine and reduced arm swing were the most frequently registered motor disorders (73%, 75%). Freezing at the start of, or during, walking was not observed during clinical testing but was frequently claimed to occur at home (48%, 23%). A broad spectrum of deficits regarding gait, posture, transfers and distal motor problems formed a cluster, which was strongly correlated with bradykinesia (p < 0.001). Principal component analysis identified four distinct problem areas: (1) axial motor performance; (2) akinetic gait problems; (3) rigidity; and (4) tremor. CONCLUSIONS: Parkinson patients, particularly in the later stages of the disease, presented with significant levels of functional disability which was mainly linked with the underlying impairment of bradykinesia.

Adult↗
PubMed1998

Local influence in linear mixed models.

The linear mixed model has become an important tool in modelling, partially due to the introduction of the SAS procedure MIXED, which made the method widely available to practising statisticians. Its growing popularity calls for data-analytic methods to check the underlying assumptions and robustness. Here, the problem of detecting influential subjects in the context of longitudinal data is considered, following the approach of local influence proposed by Cook.

Age Factors↗