Multinational trial

There are of course practical considerations in clinical research. We may find patient recruitment difficult in single centre studies and this is one of the major drivers to multicentre and multinational trials. Alternatively, we may need to relax the inclusion/exclusion criteria or lengthen the recruitment period. Unfortunately, while each of these may indeed increase the supply of patients they may also lead to increased variability that in turn will require more patients. A second issue is the size of the CRD which, if it is too small, will require a large number of patients. In such circumstances we may need to consider the use of surrogate endpoints (Section S.3.3.2). Finally, the standard deviation may be large and this can have a considerable impact on the sample size - for example, a doubling of the standard deviation leads to a four times increase in the... 

Bullock R, Touchon J, Bergman H, et al Rivastigmine and donepezil treatment in moderate to moderately severe Alzheimer s disease over a 2-year period. Curr Med Res Opin 21 1317-1327, 2005 Bums A, Rossor M, Hecker J, et al The effects of donepezil in Alzheimer s disease—results from a multinational trial. Dement Geriatr Cogn Disord 10 237-244, 1999... 

Phase 3, full-scale clinical evaluations of treatment efficacy. These will involve quite large numbers of patients, and nowadays are often multicentre and multinational trials. They are usually double-blind, placebo-controlled, comparing the new treatment with an existing proven one. 

Further evidence that donepezil is effective and well tolerated in treating symptoms of mild to moderately severe Alzheimer s disease has emerged from a multinational trial (26). Common adverse effects were nausea, vomiting, diarrhea, anorexia, dizziness, and confusion, consistent with previous findings. 

Cohn JN, Tognoni G, Glazer RD, Spormann D, Hester A. Rationale and design of the Valsartan Heart Failure Trial a large multinational trial to assess the effects of valsartan, an angiotensin-receptor blocker, on morbidity and mortality m chronic congestive heart failure. J Card Fail 1999 5(2) 155-60. 

First, the largest prospective trial to date to evaluate the diagnostic value of BNP is The Breathing Not Properly Multicenter Study, from which numerous publications have addressed multiple aspects regarding the utility of BNP monitoring. In this multinational trial, more... 

China. Japan remains focused on possible genetic differences, and continues to insist upon studies conducted in its own population as a condition for registration and approval. Regional variations, such as diet, alcohol and tobacco consumption, climate, exposure to pollution and other environmental factors, socioeconomic status, and differences in technology and health care standards, require creative planning for multinational trials. 

Comparative studies The SCoP study was a prospective, randomized, partially blinded, active-controlled, multinational trial, designed to assess the safety of sertindole in the treatment of schizophrenia under normal conditions of use risperidone was the comparator. Results are now emerging. For instance, sertindole did not increase allcause mortality, but cardiac mortality was higher and suicide attempts possibly lower with sertindole [147. The study comprised 9858 selected patients with schizophrenia, and after 14147 person-years the major findings were (i) no statistically significant difference between sertindole ( = 4905) and risperidone (n = 4904) in the two co-primary outcomes, i.e. all-cause mortality (sertindole 64 deaths, risperidone 61 deaths HR=1.12 90% Cl = 0.83, 1.5) and cardiac events... 

The AzimiLide post-Infarct survival Evaluation (ALIVE) trial (137), a doubleblind, placebo-controlled, multinational trial, assessed the effect of azimilide on survival in high-risk post myocardial infarction (within 6-21 days) and patients with left ventricular ejection fractions between 0.15 and 0.35. There was no survival advantage from azimilide but no harm caused by the dmg. 

On the other hand, in the International Tamoxifen Exemestane Adjuvant Multinational trial, patients with certain specific AEs such as vasomotor symptoms, musculoskeletal AEs and vulvovaginal symptoms (vs nonspecific or no AEs) presented superior disease-free survival, better overall survival and fewer distant metastases and may therefore be useful in predicting treatment responses in patients with breast cancer treated with endocrine therapy [30 ]. 

Fontein DB, Seynaeve C, Hadji P, HiUe ET, van de Water W, Putter H, et al. Specific adverse events predict survival benefit in patients treated with tamoxifen or aromatase inhibitors an international tamoxifen exemestane adjuvant multinational trial analysis. J CHn Oncol... 

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