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T J Cleophas

Publications and source records attributed to T J Cleophas.

At least 19 recordsLinked to original sources
PubMed1997

Clinical trials: specific problems associated with the use of a placebo control group.

The topic of placebos in clinical research has been recently addressed in general medical journals, and is relevant to a clinical pharmacologists' readership as well. In this article we try to give an overview of the benefits as well as problems of this methodology. Although the use of placebos in drug development is frequently absolutely essential, important ethical and technical problems are generally involved. We conclude that the placebo-controlled trial although methodologically pure may sometimes cause too many difficulties in the clinical setting.

Control Groups↗
PubMed1997

Comparison of multiple-dose and once-daily nitrate therapy in 1212 patients with stable angina pectoris: effects on quality of life indices. Dutch Mononitrate Quality of Life (DUMQOL) Study Group.

BACKGROUND: Nitrates, although important for the management of anginal symptoms, produce significant side effects. Little is known about their net effects on health-related, quality-of-life indices. METHODS: In a self-controlled, 6-month study, the effects on symptoms and quality of life of multiple-dose and once-daily nitrate therapy were evaluated in 1212 patients with stable angina pectoris. Quality of life was assessed by a test battery based on the exercise-tolerance index of Wiklund, the psychological well-being index of Dupuy, and the Short Form 36 questionnaire of Stewart. The internal consistency and reliability of the multi-item scales were estimated by Cronbach's alpha coefficients. RESULTS: The effects of the two treatment regimens on pain index and number of additional sublingual nitrate tablets required were not different. However, based on the New York Heart Association (NYHA) angina classification, patients improved better on the once-daily than on the multiple-dose regimen: by > 1 category in 281 vs 62 of the patients (P < 0.0001); mobility and psychological distress indices also improved (P = 0.006, and P = 0.007). CONCLUSIONS: Once-daily nitrate therapy not only provides a better NYHA angina classification than multiple-dose therapy does, but also provides a better quality of life as estimated by improvement of mobility and distress indices, the most important indicators of quality of life in this category of patients.

Activities of Daily Living↗
PubMed1997

Depression and myocardial infarction. Implications for medical prognosis and options for treatment.

Depression and myocardial infarction (MI) are closely related. Various pathophysiological mechanisms could link depression to MI, and the different pharmacological and nonpharmacological treatment modalities that could be used have both advantages and disadvantages. Unlike tricyclic antidepressants, the selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) lack arrhythmogenic effects. In addition to their beneficial effects on depression, SSRIs have positive effects on psychological factors such as anxiety and mood disturbances that are not uncommon in patients who have had an MI. Therefore, these drugs should be preferentially considered for the treatment of depression in MI patients. Studies to further determine the impact of depression on the outcome of MI, and the place of different treatment modalities, are in progress.

Anti-Arrhythmia Agents↗
PubMed1997

Phase III trials: specific problems associated with the use of a placebo control group.

The topic of placebos in clinical research has been recently addressed in general journals and is relevant to a clinical pharmacologists' readership as well. We try to give an overview of benefits as well as problems of this methodology. Although the use of placebo in drug development is frequently absolutely essential, important ethical and technical problems are generally involved. The placebo-controlled trial, although methodologically pure, may sometimes cause too much difficulties in the clinical setting.

Clinical Trials, Phase III as Topic↗
PubMed1996

Crossover trials with a binary response: a powerful method despite the carryover effect.

The two-period crossover trial has the evident advantage that, by use of within-patient comparisons, the usual large between-patient variability is not used as a measure to compare treatments. A prerequisite, however, is that the order of the treatments does not substantially influence the outcome of the treatment. Crossover studies with a binary response (such as yes/no or present/absent), although widely used for initial screening of new compounds, have not previously been studied for such order effects. This study uses a mathematical model based on standard statistical tests to study to what extent such order effects, here identical to carryover effects, may reduce the power of detecting a treatment effect. It is concluded that, despite large carryover effects, the crossover study with a binary response remains a powerful method and that testing for carryover effects makes sense only if the null hypothesis of no treatment effect cannot be rejected.

Clinical Trials as Topic↗
PubMed1996

Clinical trials: relevance of correlation between treatment responses.

OBJECTIVE: Trials that do not allow rejection of the null hypothesis of no treatment effect may have had an inappropriate design. Trials are virtually never assessed for correlation between responses to different treatment modalities. METHODS: Using a hypothetical example and several published studies we examine the influence of correlation levels between treatment modalities on the sensitivity of testing. RESULTS: The level of correlation between responses to different treatment modalities is a major determinant of the sensitivity both of crossover and parallel group clinical trials. CONCLUSIONS: It is very relevant to assess a priori correlation levels between responses to the different treatment modalities of a trial. If a negative correlation is anticipated, a crossover design is likely to lack sensitivity. If a positive correlation is anticipated a parallel-group design seems less appropriate, because it would lack the extra sensitivity of accounting for the positive correlation. Both designs would seem suitable for approximately zero correlations (e.g. comparison vs baseline or vs placebo under the assumption that the number of placebo responders is negligible.

Clinical Trials as Topic↗
PubMed1996

Crossover trials are only useful when there is a positive correlation between the response to different treatment modalities.

1. Trials that do not allow us to reject the null hypothesis of no treatment effect may have had an inappropriate design. Trials are virtually never assessed for correlation between responses to different treatment modalities. 2. The level of correlation between responses to different treatment modalities is a major determinant of the power of crossover trials. 3. It is relevant to assess correlation levels between responses to the different treatment modalities a priori. With a negative correlation a crossover design is likely to lack power. 4. In 1991 the British Journal of Clinical Pharmacology published eight crossover trials which would have been more efficient had they been performed with a parallel groups design.

Clinical Trials as Topic↗
PubMed1996

Criticism of cardiovascular studies with negative results due to a negative correlation.

BACKGROUND: Trials that do not allow rejection of the null hypothesis of no treatment effect may have had an inappropriate design. Self- controlled trials, although routinely used for the study of cardiovascular diseases, are virtually never assessed for correlation between treatment modalities. METHODS: Using three models and a series of published studies as examples, the author studies the influence of correlation levels on the statistical power of self-controlled studies. RESULTS: Between-subject variation as estimated by SD is largely dependent on the level of correlation, and so is the power of testing. The assessment of paired data as though they are unpaired can be used as a simple test to estimate correlation levels. CONCLUSION: It is extremely relevant to assess correlation levels in a paired comparison a priori. With a presumably negative correlation, a self- controlled design is likely to lack power.

Cardiovascular Diseases↗
PubMed1996

Nitrate-induced headache in patients with stable angina pectoris: beneficial effect of starting on a low dosage. 5-ISMN headache study group.

BACKGROUND: Nitrates, although important for the management of angina pectoris, cause significant headache in many patients. METHODS: In a randomized, double-blind, crossover study, 89 patients with stable angina pectoris were studied to compare two different dosage strategies of isosorbide-5-mononitrate (5-ISMN). Patients were randomized to either 60 mg 5-ISMN once daily (od) for two weeks or to 30 mg 5-ISMN od for one week followed by 60 mg 5-ISMN od for one week. Then, there was a two-week placebo washout, after which the alternative treatment was given. The authors assessed the occurrence of angina pectoris and headache by diary cards while taking into account the number of isosorbide dinitrate sublingual puffs and paracetamole tablets required. Data were assessed for carryover and time effects. RESULTS: The two dosage regimens were equally efficient for the relief of angina pectoris without development of tolerance. Thirty percent of the patients never experienced headache from the given dosages. In the remainder of them there was a highly significant time effect: the overall numbers of headache attacks in the first period of active treatment versus the second were 2,380 vs 1,400 (P < 0.003). Yet significantly fewer patients had headache on low dosage than on high dosage (45 vs 57, P < 0.02). CONCLUSIONS: (1) Starting on a low dosage was associated with a reduced frequency and severity of headache and did not notably influence the beneficial effect on angina pectoris. (2) One in 3 patients never experienced headache from the given dosages. (3) The overall number of headache attacks in the first period of active treatment was significantly higher than in the second period irrespective of the dosages given.

Adult↗
PubMed1996

Wine consumption and other dietary variables in males under 60 before and after acute myocardial infarction.

In France there are few cardiac deaths in spite of high animal fat intake. France and Italy have the highest overall intake of alcohol in the world. Obviously, there is an inverse association between coronary heart disease (CHD) and alcohol intake in these countries. Although in the past decade several-large scale population studies have confirmed the beneficial effect of alcohol on CHD, these studies may not have been sensitive to control all the confounding variables. No one so far has explored the possibility that the French may be protected by their low level of life stress. In 1993 we conducted a case-control study (n = 118) to examine psychological variables in a group of Dutch males under sixty years of age, before and after acute myocardial infarction (MI). After adjustment for total cholesterol, blood pressure, and smoking, a number of psychological factors appeared to be independently associated with an increased risk of MI. For the present study the same group of patients was assessed for consumption of different types of alcoholic beverages, coffee, sugar, high-fat diet, and vegetables. In the univariate analysis patients appeared to have consumed more red wine (odds ratio [OR] 0.2, P = 0.03) and controls more spirits (OR 4.0, P = 0.005). After adjustment for total cholesterol, blood pressure, and smoking as well as the independent psychological factors, red wine lost its significance (OR 0.4, P = 0.17) whereas the OR for spirits even rose (OR 6.0, P = 0.01). The beneficial effect of wine may be an expression of a relatively low level of life stress. Alcohol itself is not protective but rather a strong risk factor of MI.

Adult↗
PubMed1996

Quality of life before and during antihypertensive treatment: a comparative study of celiprolol and atenolol.

BACKGROUND: The well-being of hypertensive patients may be adversely affected by the disease itself, its complications, and other concomitant processes such as anxiety, sedation, and side effects of the prescribed drugs. Some recently developed antihypertensive agents have been suggested to be devoid of these deleterious effects on well-being expressed as quality of life. OBJECT: We compared the effect on quality of life of a standard cardioselective beta-blocker atenolol to the effect of celiprolol as a representative of a new class of selective beta-blockers with vasodilatory properties. One-hundred-thirty-two patients with mild to moderate hypertension were eligible to enter a 28-week double-blind parallel-group study, consisting of a 4-week run-in period on placebo and a 24-week period on dosage-adjusted treatment with either atenolol or celiprolol. RESULTS: Both systolic and diastolic blood pressure were assessed, as was quality of life perception by a selected test battery including the Quality of Life Questionnaire of Bulpitt and Fletcher [1990]. During celiprolol treatment, supine blood pressure fell from 167/101 (range 120-200/95-116) to 150/92 mm Hg (p < 0.0001). This antihypertensive effect was at least as good with celiprolol as with atenolol. Quality of life perception was comparable for the 2 drugs, although some adverse effects were more frequent during atenolol than during celiprolol, particularly after prolonged treatment. Also patient compliance was better for celiprolol than for atenolol. CONCLUSIONS: Our results show that the selective beta-blocker with vasodilatory property celiprolol is at least as effective as atenolol and that it has additional advantage in terms of enhancement of some quality of life variables.

Adult↗