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Biomedical subjects

Michel Cucherat

Publications and source records attributed to Michel Cucherat.

At least 19 recordsLinked to original sources
PubMed2006

Angiotensin-converting enzyme inhibitors in patients with coronary artery disease and absence of heart failure or left ventricular systolic dysfunction: an overview of long-term randomized controlled trials.

BACKGROUND: Results of randomized trials of angiotensin-converting enzyme inhibitors in patients with coronary artery disease (CAD) and preserved left ventricular function are conflicting. We undertook this study to determine whether long-term prescription of angiotensin-converting enzyme inhibitors decreases major cardiovascular events and mortality in patients who have CAD and no evidence of left ventricular systolic dysfunction. METHODS: We searched MEDLINE, EMBASE, and IPA databases, the Cochrane Controlled Trials Register (1990-2004), and reports from scientific meetings (2003-2004), and we reviewed secondary sources. Search terms included angiotensin-converting enzyme inhibitors, coronary artery disease, randomi(s)zed controlled trials, clinical trials, and myocardial infarction. Eligible studies included randomized controlled trials in patients who had CAD and no heart failure or left ventricular dysfunction, with follow-up omicronf 2 years or longer. Of 1146 publications screened, 7 met our selection criteria and included a total of 33 960 patients followed up for a mean of 4.4 years. RESULTS: Five trials included only patients with documented CAD. One trial included patients with documented CAD (80%) or patients who had diabetes mellitus and 1 or more additional risk factors, and another trial included patients who had CAD, a history of transient ischemic attack, or intermittent claudication. Treatment with angiotensin-converting enzyme inhibitors decreased overall mortality (odds ratio, 0.86; 95% confidence interval, 0.79-0.93), cardiovascular mortality (odds ratio, 0.81; 95% confidence interval, 0.73-0.90), myocardial infarction (odds ratio, 0.82; 95% confidence interval, 0.75-0.89), and stroke (odds ratio, 0.77; 95% confidence interval, 0.66-0.88). Other end points, including resuscitation after cardiac arrest, myocardial revascularization, and hospitalization because of heart failure, were also reduced. CONCLUSION: Angiotensin-converting enzyme inhibitors reduce total mortality and major cardiovascular end points in patients who have CAD and no left ventricular systolic dysfunction or heart failure.

Aged↗
PubMed2006

A new obstetric forceps for the training of junior doctors: a comparison of the spatial dispersion of forceps blade trajectories between junior and senior obstetricians.

OBJECTIVE: The purpose of this study was to create a new instrument for the training of doctors in the use of forceps and to compare the trajectories of forceps blades between junior and senior obstetricians. STUDY DESIGN: We equipped a simulator and forceps with spatial location sensors. The head of the fetus was in an occipitoanterior location, at a "+5" station. Forceps blade trajectories were analyzed subjectively with the 3-dimensional spatial graph and objectively based on 3 points of special interest. Each obstetrician performed 4 forceps blades placements. We compared the trajectories of junior and senior obstetricians. RESULTS: For senior operators, spatial dispersion was "excellent," "very good," or "good" in 92% of cases, whereas this was the case for only 38% of junior doctors (92% vs 38%; P < .001). CONCLUSION: A new instrument has been designed to demonstrate the trajectory of forceps blades during application in a simulator. The instrument captures the difference in experience between senior and junior clinicians.

Computer Simulation↗
PubMed2006

Procalcitonin as a diagnostic test for sepsis in critically ill adults and after surgery or trauma: a systematic review and meta-analysis.

OBJECTIVE: To quantify the accuracy of serum procalcitonin as a diagnostic test for sepsis, severe sepsis, or septic shock in adults in intensive care units or after surgery or trauma, alone and compared with C-reactive protein. To draw and compare the summary receiver operating characteristics curves for procalcitonin and C-reactive protein from the literature. DATA SOURCE: MEDLINE (keywords: procalcitonin, intensive care, sepsis, postoperative sepsis, trauma); screening of the literature. STUDY SELECTION: Meta-analysis of all 49 published studies in medical, surgical, or polyvalent intensive care units or postoperative wards. Children, medical patients, and immunocompromised patients were excluded. DATA EXTRACTION: Thirty-three studies fulfilled inclusion criteria (3,943 patients, 1,828 males, 922 females; mean age: 56.1 yrs; 1,825 patients with sepsis, severe sepsis, or septic shock; 1,545 with only systemic inflammatory response syndrome); eight studies could not be analyzed statistically. Global mortality rate was 29.3%. DATA SYNTHESIS: Global odds ratios for diagnosis of infection complicated by systemic inflammation were 15.7 for the 25 studies (2,966 patients) using procalcitonin (95% confidence interval, 9.1-27.1) and 5.4 for the 15 studies (1,322 patients) using C-reactive protein (95% confidence interval, 3.2-9.2). The summary receiver operating characteristics curve for procalcitonin was better than for C-reactive protein. In the 15 studies using both markers, the Q* value (intersection of summary receiver operating characteristics curve with the diagonal line where sensitivity equals specificity) was significantly higher for procalcitonin than for C-reactive protein (0.78 vs. 0.71, p = .02), the former test showing better accuracy. CONCLUSIONS: Procalcitonin represents a good biological diagnostic marker for sepsis, severe sepsis, or septic shock, difficult diagnoses in critically ill patients. Procalcitonin is superior to C-reactive protein. Procalcitonin should be included in diagnostic guidelines for sepsis and in clinical practice in intensive care units.

Adult↗
PubMed2006

Compliance-guided therapy : a new insight into the potential role of clinical pharmacologists.

BACKGROUND AND OBJECTIVE: In the field of drug noncompliance, we investigated an original approach that could give the prescribing physician, in collaboration with a clinical pharmacologist, an active role. The aim here is for the prescribing physician to take compliance into account so as to provide an optimised prescription (choice of molecule prescribed and its rhythm of administration) adapted to each patient. The example considered is that of oral anticoagulant treatment prescribed long-term. METHODS: In order to investigate the choice of the best molecule and treatment regimen for a given noncompliance pattern, we performed an in silico study with two oral anticoagulant agents, warfarin and acenocoumarol, each taken in one or two daily doses. Three linked models were used: the first model generated specific noncompliance patterns, the second model described the pharmacokinetics of oral anticoagulant agents and the third model summarised the pharmacokinetic-pharmacodynamic relations. RESULTS: Considering different patterns of noncompliance (including timing errors in drug intake and the phenomenon of drug holidays) and comparing warfarin with acenocoumarol, we identified different situations in which one agent (prescribed once or twice daily) could clearly minimise both the thromboembolic and haemorrhagic risks. However, for some specific noncompliance patterns, the choice of the optimal therapy should also be guided by the basal individual thromboembolic and haemorrhagic risks. CONCLUSION: Individualisation of drug therapy involves both drug dose and drug choice. In addition to the classical approach (i.e. drug level measurements, enzyme assays and even genetic sequence data), our study suggests that compliance-guided therapy may represent a potential, evolving way for the individualisation of prescriptions.

Humans↗
PubMed2005

Birth simulator: reliability of transvaginal assessment of fetal head station as defined by the American College of Obstetricians and Gynecologists classification.

OBJECTIVE: This study was undertaken to investigate the reliability of transvaginal assessment of fetal head station by using a newly designed birth simulator. STUDY DESIGN: This prospective study involved 32 residents and 25 attending physicians. Each operator was given all 11 possible fetal stations in random order. A fetal head mannequin was placed in 1 of the 11 American College of Obstetricians and Gynecologists (ACOG) stations (-5 to +5) in a birth simulator equipped with real-time miniaturized sensor. The operator then determined head position clinically using the ACOG classification. Head position was described as: (1) "engaged" or "nonengaged" (engagement code); (2) "high," "mid," "low," or "outlet" (group code); and (3) according to the 11 ACOG ischial spine stations (numerical code). Errors were defined as differences between the stations given by the sensor and by the operator. We determined the error rates for the 3 codes. RESULTS: "Numerical" errors occurred in 50% to 88% of cases for residents and in 36% to 80% of cases for attending physicians, depending on the position. The mean "group" error was 30% (95% CI 25%-35%) for residents and 34% (95% CI 27%-41%) for attending physicians. In most cases (87.5% for residents and 66.8% for attending physicians) of misdiagnosis of "high" station, the "mid" station was retained. Residents and attending physicians made an average of 12% of "engagement" errors, equally distributed between false diagnosis of engagement and nonengagement. CONCLUSION: Our results show that transvaginal assessment of fetal head station is poorly reliable, meaning clinical training should be promoted. The choice not to perform vaginal delivery when the fetus is in the "mid" position strongly decreases the risk of applying instruments on an undiagnosed "high" station. Conversely, obstetricians who perform only "low" operative vaginal deliveries also deliver unrecognized "mid" station fetuses. Therefore, residency programs should offer training in "mid" pelvic operative vaginal deliveries. Birth simulators could be used in training programs.

Delivery, Obstetric↗
PubMed2005

The true treatment benefit is unpredictable in clinical trials using surrogate outcome measured with diagnostic tests.

BACKGROUND AND OBJECTIVES: Clinical trials increasingly use results of diagnostic tests as surrogate outcomes. Our objective was to answer the following questions: (1) is the parameter measured by the reference standard a valid surrogate? (2) How does the tests accuracy influence the estimate of the treatment benefit on surrogate? (3) Is it possible to correct the measured treatment effect given by results of inaccurate tests? METHODS AND SETTING: We reviewed the literature on asymptomatic deep venous thrombosis (DVT), detected by the reference standard and other imaging techniques, as surrogate for venous thromboembolism. The influence of test inaccuracy on the measurement of treatment benefit was calculated as a function of the patient baseline risk, the treatment effect model, and test performances. RESULTS: We show that: (1) asymptomatic DVT is correlated with clinical outcomes but is yet to be established as a surrogate; (2) inaccurate diagnostic test underestimates the treatment effect on surrogate; (3) the prevalence of the disease, the treatment effect model, and the accuracy of the test and the reference standard used to evaluate it need to be known to correct this underestimation. CONCLUSION: Even when the surrogate end point is valid, without a reliable study of the diagnostic test we cannot quantify the true treatment effect.

Biomarkers↗
PubMed2005

How to measure non-consistency of medical practices with available evidence in therapeutics: a methodological framework.

Since the early 1980s many studies showed a gap between available evidence and medical practice. They were designed to assess the real impact of randomized clinical trials on the practice of medicine. Their results substantiated a knowledge translation problem. However, they were qualitative findings, i.e. a gap exists or not, although the problem is quantitative (how large is the gap?) and has several components that should be documented according to the objective of the study. In this article, we explored the components and the various contexts in which the measure of the distance between practice and knowledge is considered. All these features should be taken into account for a more accurate and relevant assessment of the distance.

Clinical Competence↗
PubMed2005

Comparison of the efficacy of cooled-tip and 8-mm-tip catheters for radiofrequency catheter ablation of the cavotricuspid isthmus: a meta-analysis.

BACKGROUND: Cooled-tip RFA (cRFA) and conventional 8-mm-tip catheters were found to be more effective and as safe as conventional 4-mm-tip catheters for atrial flutter (AFL) radiofrequency ablation (RFA), facilitating the rapid achievement of bi-directional isthmus block (BIB), but studies comparing cRFA and 8-mm-tip catheters are not randomized or results are discussed. Thus, we performed a meta-analysis of available randomized trials to evaluate the effectiveness in terms of primary success and procedure parameters. METHODS: Reports of trials were identified through a Medline, Embase, Current Contents, Cardline, and an extensive bibliography search. Trials that met the following criteria were included: (1) prospective, randomized, controlled, and open trials; (2) patients assigned to an 8-mm-tip or a cRFA catheter for AFL RFA; (3) endpoints events related to primary success rate (BIB achievement), and procedure parameters (number of RF applications, x-ray exposure and ablation duration). RESULTS: Seven trials met the inclusion criteria. They included 603 patients with established AFL randomized to an 8-mm-tip or cRFA catheter group. Comparing 8-mm groups with cRFA groups, the meta-analysis showed similar BIB achievement relative risk (RR) 0.96, 95% confidence interval (CI): 0.92 to 1.01, (P = 0.13); total RF application time weighted mean difference (WMD) 0.88, 95% CI: -0.36 to 2.12, (P = 0.16); duration of x-ray exposure (min) (WMD = 1.07, 95% CI: -0.81 to 0.295, (P = 0.26); ablation procedure duration (min) (WMD = 0.68, 95% CI: -3.37 to 4.73; P = 0.74). CONCLUSION: The present meta-analysis confirms that cooled-tip and large-tip catheters are equally efficient for cavotricuspid isthmus ablation with both similar primary success rates and procedure parameters.

Aged↗
PubMed2004

Bridging the gap between therapeutic research results and physician prescribing decisions: knowledge transfer, a prerequisite to knowledge translation.

BACKGROUND: A wide gap continues to exist between available therapeutic research results and physician's prescribing. Numerous explanations account for this gap, but one central reason is the difficulty in transferring comprehensive research information to practicing clinicians. This problem arises from information overload and the growing complexity of research findings. We propose a multistep process that can be used to develop systems to bridge this information/prescription gap. The steps include: comprehensively collecting and summarizing clinical trial reports, scoring and ranking these according to their level of evidence, exploring and synthesizing the data using meta-analyses, summarizing these results, representing them in an easily understandable form, and transmitting the overview findings to prescribers at the time they need them. DISCUSSION: This ambitious endeavor is needed to ensure that prescribers have access to pertinent research results for use in their prescription decisions. We demonstrate in this article that there are no theoretical or technical obstacles to make the proposed system workable.

Clinical Competence↗
PubMed2004

Microvessel density as a prognostic factor in women with breast cancer: a systematic review of the literature and meta-analysis.

We performed a meta-analysis of all 87 published studies linking intratumoral microvessel density (MVD), reflecting angiogenesis, to relapse-free survival (RFS) and overall survival (OS). With median MVD as cutoff, MVD impact was measured by risk ratio (RR) between the two survival distributions. Seventeen studies did not mention survival data or fit inclusion criteria. Twenty-two were multiple publications of the same series, leaving 43 independent studies (8936 patients). MVD was assessed by immunohistochemistry, using antibodies against factor VIII (27 studies; n = 5262), CD31 (10 studies; n = 2296), or CD34 (8 studies; n = 1726). MVD might be a better prognostic factor when assessed by CD31 or CD34 versus factor VIII (P = 0.11). For RFS, statistical calculations were performed in 25 studies (6501 patients). High MVD significantly predicted poor survival [RR = 1.54 for RFS and OS with the same 95% confidence interval (CI), 1.29-1.84]. Twenty-two studies analyzed separately lymph node-negative patients (n = 3580), for whom predictors of poor survival are requested. This latter meta-analysis included 15 studies for RFS (2727 patients) and 11 for OS (1926 patients). High MVD significantly predicted poor survival [RR = 1.99 for RFS (95% CI, 1.33-2.98) and RR = 1.54 for OS (95% CI, 1.01-2.33)]. Between-study variations could result from patient selection criteria, techniques to stain and count microvessels, and cutoff selection. MVD was a significant although weak prognostic factor in women with breast cancer. Standardization of MVD assessment is needed.

ADP-ribosyl Cyclase↗
PubMed2004

Perioperative outcome and long-term survival of surgery for acute post-infarction mitral regurgitation.

OBJECTIVE: To determine factors predictive of mortality in patients undergoing emergency mitral valve surgery in the setting of severe post-infarction regurgitation. METHODS: Patients admitted for an acute myocardial infarction who required urgent mitral valve surgery for severe regurgitation were studied. Factors predictive of outcome were analysed. RESULTS: Fifty-five consecutive patients (mean 65+/-10 years, 37 males) were included. The infarct was inferior in 31 patients, posterior in 10, anterior in 9 and lateral in 5. Thirty-four patients (62%) were in Killip class IV. Peroperative findings confirmed total papillary muscle rupture in 25 patients (posteromedial in 21, anterolateral in 4), and partial rupture in 12 patients (posteromedial in 10, anterolateral in 2). Papillary muscle dysfunction without rupture was responsible for regurgitation in 18 patients (posteromedial in 15, anterolateral in 3). The mitral valve was replaced by a prosthesis in all but 4 patients, who had valvuloplasty. Coronary angiography was done in 32 patients, of whom 18 underwent concomitant coronary artery bypass grafting and 2 balloon angioplasty. Surgery was performed on average 7 days after infarction. Thirteen patients (24%) died during the perioperative period. Absence of coronary revascularisation was significantly associated with increased perioperative mortality (34% vs. 9%, P = 0.02). Of the 42 surviving patients, there were 5 deaths during a mean follow-up of 4.0+/-3.7 years. CONCLUSION: In patients with acute post-infarction mitral regurgitation, perioperative mortality is high, but can be improved with concomitant CABG in addition to valve surgery. Long-term outcome of survivors is favourable.

Acute Disease↗
PubMed2004

Mathematical modelling of an ischemic stroke: an integrative approach.

Understanding the mechanisms and the time and spatial evolution of penumbra following an ischemic stroke is crucially important for developing therapeutics aimed at preventing this area from evolving towards infarction. To help in integrating the available data, we decided to build a formal model. We first collected and categorised the major available evidence from animal models and human observations and summarized this knowledge in a flow-chart with the potential key components of an evolving stroke. Components were grouped in ten sub-models that could be modelled and tested independently: the sub-models of tissue reactions, ionic movements, oedema development, glutamate excitotoxicity, spreading depression, NO synthesis, inflammation, necrosis, apoptosis, and reperfusion. Then, we figured out markers, identified mediators and chose the level of complexity to model these sub-models. We first applied this integrative approach to build a model based on cytotoxic oedema development following a stroke. Although this model includes only three sub-models and would need to integrate more mechanisms in each of these sub-models, the characteristics and the time and spatial evolution of penumbra obtained by simulation are qualitatively and, to some extent, quantitatively consistent with those observed using medical imaging after a permanent occlusion or after an occlusion followed by a reperfusion.

Animals↗
PubMed2004

A systematic review of the accuracy of ultrasound in the diagnosis of deep venous thrombosis in asymptomatic patients.

Evaluation of the accuracy of ultrasound has yielded heterogeneous results. Our objective was to summarize the evidence on the accuracy of ultrasound compared to venography in asymptomatic patients, taking into account the variation due to threshold differences. Searches of journal table of contents, computer databases (Medline, Embase, Biomed, Cochrane) and conference proceedings were performed. A study was eligible if it prospectively compared ultrasound to venography for the diagnosis of DVT in asymptomatic patients. Data of studies selected for inclusion were extracted independently by two authors. High quality studies with consecutive patient enrollment, blind evaluation of the two techniques, and absence of verification bias are summarized as Level 1, while those not fulfilling one or more of these criteria are considered Level 2. Original study authors were contacted to confirm accuracy and to provide missing data. A pooled estimate of the accuracy of ultrasound was obtained according to the method of Moses and coworkers. This method gives a summary diagnostic odds ratio (DOR). The DOR is a single indicator of test performance. It varies between 0 and infinity and exceeds 1, only when ultrasound is more often positive in patients with DVT relative to those without DVT. Higher DOR indicates better discriminatory test performance. Thirty one studies were rated as potentially unbiased and graded as Level 1. The mean prevalence of DVT as determined by venography was 22%. In Level 1 studies, the odds of positive ultrasound in proximal veins was 379 times higher (95% confidence limits 65, 2,200) and in distal veins 32 times higher (7.5, 135) among patients with DVT than those without. Our results suggest that, particularly for proximal veins, ultrasound is accurate for the diagnosis of DVT in asymptomatic postoperative orthopedic patients. More research is needed in other clinical settings.

Humans↗
PubMed2003

Structural and symptomatic efficacy of glucosamine and chondroitin in knee osteoarthritis: a comprehensive meta-analysis.

OBJECTIVE: To assess the structural and symptomatic efficacy of oral glucosamine sulfate and chondroitin sulfate in knee osteoarthritis through independent meta-analyses of their effects on joint space narrowing, Lequesne Index, Western Ontario MacMaster University Osteoarthritis Index (WOMAC), visual analog scale for pain, mobility, safety, and response to treatment. METHODS: An exhaustive systematic research of randomized, placebo-controlled clinical trials published or performed between January 1980 and March 2002 that assessed the efficacy of oral glucosamine or chondroitin on gonarthrosis was performed using MEDLINE, PREMEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Current Contents, BIOSIS Previews, HealthSTAR, EBM Reviews, manual review of the literature and congressional abstracts, and direct contact with the authors and manufacturers of glucosamine and chondroitin. Inclusion, quality scoring, and data abstraction were performed systematically by 2 independent reviewers who were blinded to sources and authors. Conservative approaches were used for clear assessment of potential efficacy. RESULTS: Our results demonstrated a highly significant efficacy of glucosamine on all outcomes, including joint space narrowing and WOMAC. Chondroitin was found to be effective on Lequesne Index, visual analog scale pain, mobility, and responding status. Safety was excellent for both compounds. CONCLUSIONS: Our study demonstrates the structural efficacy of glucosamine and indistinguishable symptomatic efficacies for both compounds. Regarding the relatively sparse data on glucosamine and joint space narrowing and the absence of data on structural effects of chondroitin, further studies are needed to investigate the relationship among time, dose, patient baseline characteristics, and structural efficacy for an accurate, disease-modifying characterization of these 2 compounds.

Administration, Oral↗
PubMed2003

Amiodarone versus placebo and class Ic drugs for cardioversion of recent-onset atrial fibrillation: a meta-analysis.

OBJECTIVES: This meta-analysis compared amiodarone with placebo and class Ic drugs for the cardioversion of recent-onset atrial fibrillation (AF), defined as lasting less than seven days. BACKGROUND: Despite the lack of trials that support its efficacy convincingly, amiodarone is widely used for conversion of recent-onset AF. METHODS: We searched Medline and EMBASE databases, as well as the Cochrane Controlled Trials Register for randomized trials on recent-onset AF comparing amiodarone to placebo or class Ic drugs. Data were combined according to a fixed effect model. The primary end point was the rate of conversion at 24 h. To study time-dependency of the drugs, efficacy at 1 to 2 h, 3 to 5 h, 6 to 8 h, and at 24 h was analyzed. RESULTS: We found six studies randomizing amiodarone versus placebo (595 patients) and seven studies versus class Ic drugs (579 patients). There was no significant difference between amiodarone and placebo at 1 to 2 h, but significant efficacy was found after 6 to 8 h (relative risk [RR] 1.23, p = 0.022) and at 24 h (RR 1.44, p < 0.001). Efficacy with amiodarone was inferior to class Ic drugs for up to 8 h (RR 0.67, p < 0.001) but no difference was seen at 24 h (RR 0.95, p = 0.50). There were no major adverse effects. CONCLUSIONS: Amiodarone is superior to placebo for cardioversion of AF, and even though the onset of conversion is delayed, its efficacy is similar at 24 h compared with class Ic drugs. These results favor amiodarone as a reasonable alternative for patients with recent AF in whom class Ic and other, more rapidly acting antiarrhythmic drugs cannot be used.

Adult↗
PubMed2003

Absolute benefit, number needed to treat and gain in life expectancy: which efficacy indices for measuring the treatment benefit?

The absolute benefit (AB) is extensively used to summarize the results of clinical trials. As the AB depends directly on the patient's baseline risk, therapeutic decisions based on AB tend to favor patients at high risk. To evaluate the consequences of this decision's procedure for life-long therapy, we compare the AB with the gain in event-free life expectancy in a simulated hypertensive population. Our results show that the AB goes through a maximum and then declines as the duration of treatment increases. The amplitude of the variation of AB is independent of the baseline risks but the maximum is reached more quickly in the high-risk patients. Considering the gain in event-free life expectancy, low-risk patients benefit more than high-risk patients do, at the expense of a longer treatment exposure. The interpretation of the AB changes depending on follow-up.

Adult↗
PubMed2003

Planning and monitoring of placebo-controlled survival trials: comparison of the triangular test with usual interim analyses methods.

AIMS: For ethical and economic reasons, interim analysis of phase III clinical trials is essential. This study was conducted to compare the efficiency of two interim analysis procedures, which could be used to allow early termination of a clinical trial. METHODS: We made a post hoc application of two interim analysis methods (Lan & DeMets with O'Brien-Flemming modification, and the triangular test according to Whitehead) by using individual patient data from four published placebo-controlled survival trials. We determined the date the trial would have been stopped had each method been used, and we estimated consequent results in terms of events and patient numbers included in the trial, the duration of the trial, and on treatment effect. RESULTS: The triangular test provided the lowest number of events required to reach a conclusion of the trials while providing an accurate estimate of experimental treatment effects. The triangular test thus indicated the smallest number of patients that would have been enrolled, and the shortest trial duration. The difference between the methods was most important with a detrimental effect of experimental treatment: the number of required events was reduced by 75% and the trial duration was shortened by 48% with the triangular test compared to the Lan & DeMets method. CONCLUSIONS: Stopping a trial early must depend on the clinical context. It is most important to stop a placebo-controlled trial as soon as possible when the experimental treatment can be shown deleterious. In such a situation the triangular test is more appropriate than the Lan & DeMets method. When a treatment effect is no different from, or better than, placebo the triangular test is also superior but the importance of premature termination of the trial in such cases has to be balanced against the inevitable reduction of information that the trial can provide.

Clinical Trials, Phase III as Topic↗