Patient based method of assessing adverse events in clinical trials in rheumatology: the revised Stanford Toxicity Index

We describe the progress towards developing a patient rated toxicity index that meets all of the patient-important attributes defined by the OMERACT Drug Safety Working Party, These attributes are frequency, severity. importance to patient, importance to the clinician, impact on economics, impact on activities, and integration of adverse effects with benefits. The Stanford Toxicity Index (STI) has been revised to collect all attributes with the exception of impact on activities. However, since the STI is a part of the Health Assessment Questionnaire (HAQ). impact on activities is collected by the HAQ. In particular, a new question asks patients to rate overall satisfaction, taking into consideration both benefits and adverse effects. The nest step in the development of this tool is to ensure that the STI meets the OMERACT filter of truth, discrimination, and feasibility. Although truth and feasibility have been confirmed by comparisons within the ARAMIS database, discrimination needs to be assessed in clinical trials.

Clinical trials with glycoprotein IIB/IIIA antagonists - No benefit without bleeding?

As the glycoprotein GPIIb/IIIa receptor is the final common pathway in platelet aggregation, antagonists of this receptor cause a profound inhibition of aggregation induced by any agonist. The short-term efficacy and safety of GPIIb/IIIa antagonists in patients undergoing coronary angioplasty was demonstrated with murine 7E3 Fab, but this antibody was immunogenic. Abciximab is a chimeric human-mouse monoclonal antibody that is less immunogenic. The first major trial with a GPIIb/IIIa antagonist was the EPIC trial with abciximab, which showed that abciximab reduced the ischemic complications of coronary balloon angioplasty and atherectomy in high-risk patients, but increased the risk of bleeding. Subsequent studies showed that using less concurrent heparin reduced bleeding. Abciximab also reduced the rate of revascularization. Further studies have shown that the benefits of abciximab extended to all patients undergoing angioplasty (EPILOG), including patients with unstable angina (CAPTURE) and acute myocardial infarction (RAPPORT). Clinical trials with eptifibatide and tirofiban have failed to demonstrate benefit, at the doses used, in angioplasty. Abciximab and eptifibatide, but not oral xemilofiban, improve the safety of the coronary stenting procedure. Shortterm intravenous treatment with lamifiban, eptifibatide or tirofiban is beneficial in acute coronary syndromes (unstable angina, non-Q wave myocardial infarction). Orally active GPIIb/IIIa antagonists are being developed for use in acute coronary syndromes and myocardial infarction. However, no benefit has been shown with lefradafiban in acute coronary syndromes and sibrafiban and orbofiban are harmful. Eptifibatide, lamifiban and abciximab improve coronary patency in myocardial infarction, and long-term trials of GPIIb/IIIa antagonists are being conducted in acute myocardial infarction. Abciximab can cause thrombocytopenia, and all the GPIIb/IIIa antagonists increase the incidence of bleeding, but there is no excess of intracranial hemorrhage. (C) 2001 Prous Science. All rights reserved.

Randomisation in clinical trials

Randomisation is the process of assigning clinical trial participants to treatment groups. Randomisation gives each participant a known (usually equal) chance of being assigned to any of the groups. Successful randomisation requires that group assignment cannot be predicted in advance.

Outcome variables for osteoarthritis clinical trials: the OMERACT-OARSI set of responder criteria

Improvement in analysis and reporting results of osteoarthritis (OA) clinical trials has been recently obtained because of harmonization and standardization of the selection of outcome variables (OMERACT 3 and OARSI). Moreover, OARSI has recently proposed the OARSI responder criteria. This composite index permits presentation of results of symptom modifying clinical trials in OA based on individual patient responses (responder yes/no). The 2 organizations (OMERACT and OARSI) established. a task force aimed at evaluating: (1) the variability of observed placebo and active treatment effects using the OARSI responder criteria; and (2) the possibility of proposing a simplified set of criteria. The conclusions of the task force were presented and discussed during the OMERACT 6 conference, where a simplified set of responder criteria (OMERACT-OARSI set of criteria) was proposed.

The comprehensive osteoarthritis test: a simple index for measurement of treatment effects in clinical trials

Objective. To assess the measurement properties of a simple index of symptom severity in osteoarthritis (OA) of the hips and knees. Methods. Both the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the proposed new Comprehensive Osteoarthritis Test (COAT) instrument were completed weekly by 125 subjects in the context of a randomized, 12-week, 3 parallel-arm clinical trial. The reliabilities of the various scales were assessed on a weekly basis by use of Cronbach's alpha coefficients. The validity of the COAT total scale was assessed by correlation with the WOMAC total scale on a weekly basis with correlation coefficients, and in terms of the correlations between subject-level intercepts and slopes over time. The relative responsiveness of the WOMAC and COAT total scales was assessed using a multilevel (longitudinal) multivariate (WOMAC, COAT) linear model. Results. The WOMAC and COAT total scales were highly reliable (mean over weeks: WOMAC alpha = 0.98; COAT alpha = 0.97). The correlations between the WOMAC and COAT scales were very high (mean over weeks = 0.92; subject-level intercepts = 0.91, slopes = 0.88). The COAT total scale was significantly more responsive than the WOMAC total scale in the active treatment (34.8% improvement vs 26.8%; p = 0.002). Conclusion. The COAT total scale is simple to administer, reliable, valid, and responsive to treatment effects.

A systematic review and meta-analysis of clinical trials on physical interventions for lateral epicondylalgia

A systematic review of the literature on the effectiveness of physical interventions for lateral epicondylalgia ( tennis elbow) was carried out. Seventy six randomised controlled trials were identified, 28 of which satisfied the minimum criteria for meta-analysis. The evidence suggests that extracorporeal shock wave therapy is not beneficial in the treatment of tennis elbow. There is a lack of evidence for the long term benefit of physical interventions in general. However, further research with long term follow up into manipulation and exercise as treatments is indicated.

Comparison of clinical trials with sildenafil, vardenafil and tadalafil in erectile dysfunction

Erectile dysfunction (ED) affects up to 50% of men, between 40 and 70 years of age. In the first major trial of sildenafil in ED, at 24 weeks, improved erections were reported by 77 and 84% of men taking sildenafil 50 and 100 mg, respectively. Subsequently, sildenafil has been reported to be effective in men with ED associated with diabetes and prostate cancer, and in psychogenic ED. Sildenafil is safe in men with coronary artery disease, provided it is not used with the nitrates (a contraindication). The most commonly reported adverse effects with sildenafil are headache, flushing and dyspepsia. Vardenafil is more potent and more selective than sildenafil at inhibiting phosphodiesterase-5. Vardenafil is similarly effective to sildenafil in the treatment of ED. The only advantage that vardenafil has over sildenafil is that it does not inhibit phosphodiesterase-6 to alter colour perception, a rare side effect which sometimes occurs with sildenafil. Tadalafil has a longer duration of action than sildenafil and vardenafil. Tadalafil is similarly effective as sildenafil in the treatment of ED. In comparison studies, tadalafil is preferred to sildenafil (50/100 mg) by men with ED, possibly because of its longer duration of action. of the phosphodiesterase inhibitors, tadalafil may displace sildenafil as the drug of choice among men with ED.