Double-blind study, definition

A randomised, double-blind study in patients with sepsis showed the following incidence of definite nephrotoxicity ... 

Performs zero- and double-blind studies. Intralaboratory reproducibility (including ruggedness and robustness for real samples) should be demonstrated additional validation using an authentic standard reference material of the analyte in the sample matrix. Definition of criteria for revalidation. 

The question whether lutein and zeaxanthin can contribute to lowering the risk for AMD cannot be answered unequivocally by epidemiological studies. Only randomized controlled trials (RCTs) during the course of which xanthophylls are supplemented in a double-blind, placebo-controlled, and randomized manner, and in which results are evaluated according to clear predefined efficacy criteria (Seddon and Hennekens 1994) have the potential to provide definitive answers. The specific long-term time-course and intricate nature of AMD make the design of such studies difficult, however. 

The data supporting the long-term efficacy of carbamazepine are strong and substantial in some respects, but controversial and lacking definitive confirmation in others. As outlined in Table 6-2, a group of studies present data on carbamazepine prophylaxis with some degree of control in terms of randomization or blindness. With a few exceptions [Bellaire et al. 1990 Elphick et al. 1988 Placidi et al. 1986], most studies reported carbamazepine to be of equal efficacy compared with that of lithium. The response rate in these double-blind or partially controlled studies is also similar to the rate reported in the larger open literature. 

Valproate, a simple branched-chain fatty acid, was first reported as a successful treatment for acute mania by Lambert and colleagues in 1966. Following this report, at least 16 uncontrolled trials consistently supported the observation that valproate has acute and long-term mood-stabilizing effects in patients with bipolar disorder (reviewed by Keck et al. 1992a). Recently, five double-blind controlled studies of valproate have been completed that provide definitive evidence of its efficacy in acute mania. 

Phase III studies represent the confirmatory phase of drug development, which takes several years and usually involves several thousand patients at multiple trial centers. Large patient numbers are required in these trials to provide convincing documentation of clinical efficacy and safety, a more complete adverse event profile and covariates and estimates of variability in dose response relationship due to individual differences in pharmacokinetics and pharmacodynamics. They are aimed at definitively determining a drug s effectiveness and side-effect profile. Most of these studies are double-blind and placebo-controlled, sometimes with the option of open-label long-term extensions. 

Observational studies with SLIT in humans with AD claimed favorable results [48-50], However, these studies do not allow definitive conclusions and so far the amount and quality of information regarding this issue are not sufficient to formulate any formal recommendation if not that of an urgent need of properly double-blind, placebo-controlled studies. 

In a 12-week, double-blind, randomized, placebo-controlled study in 40 patients with treatment-resistant schizophrenia (funded by Johnson Johnson Pharmaceutical Research Development), the addition of risperidone to clozapine improved overall symptoms and positive and negative symptoms (49). The adverse events profile of clozapine + risperidone was similar to that of clozapine + placebo. Clozapine + risperidone did not cause additional weight gain, agranulocytosis, or seizures compared with clozapine + placebo. All the patients completed 12 weeks of treatment however, the small sample size precluded definitive conclusions. 

That vigabatrin can cause psychosis and depression has been confirmed in an analysis of data from double-blind, controlled, add-on trials (675). Compared with placebo, vigabatrin-exposed patients had a significantly higher incidence of events coded as depression (12 versus 3.5%) and psychosis (2.5 versus 0.3%). Although these events occurred during the first 3 months, most of the studies lasted 12-18 weeks and therefore definite conclusions could not be reached about timing. 

Celecoxib and rofecoxib have also been studied in AD. Randomized double blind, placebo controlled trials failed to demonstrate a therapeutic benefit (Sainetti et al., 2000 Aisen et al., 2003). The rofecoxib trial used naproxen as a control the results were consistent with other studies in which nonselective NSAIDs such as diclofenac, have been ineffective in AD (Scharf et al., 1999). Other NSAIDs including ibuprofen, indomethacin and sulindac sulfide have demonstrated potential efficacy in AD (Rogers et al., 1993 t Veld et al., 2001), but definitive trials have not yet been conducted. 

In a phase-2, partly randomized, double-blind, placebo-controlled study of three different doses of abetimus in 58 patients, seven did not receive all doses because of adverse events (2). Five withdrew because of adverse events related to their lupus erythematosus non-renal exacerbations (n = 2), hematuria and hypertension (n — 1), worsening rash (n — 1), and nephritis (n — 1). One patient withdrew because of cellulitis and another because of a localized Herpes zoster infection. None of the reported adverse events was considered to be definitely related to the drug. 

Because there have been no double-blind, placebo-controlled intervention studies of the effect of folic acid, the question of whether folic acid in patients with vitamin B12 deficiency aggravates the neurological complications cannot be answered definitively. From the data at hand we cannot exclude the possibility that folic acid may exacerbate the effects of vitamin B12 deficiency. For that reason an upper limit of 1 mg/day folic acid... 

As with other clinical studies, the most definitive clinical assessments are accomplished by double-blind, controlled trials. However investigators should consider that oral provocation of sensitive subjects could result in severe reactions and therefore study conditions should be carefully designed and controlled. 

Several clinical trials of isotretinoin have been initiated. Ongoing studies in advanced cancers include chronic myelogenous leukemia, carcinoma of the head and neck, and myelodysplastic syndromes. Adjuvant therapy trials are ongoing in non-small cell lung cancer, head and neck carcinoma, and malignant melanoma. Most of these trials utilize a randomized double-blind design. Unfortunately, for most of these studies (especially the adjuvant trials) definitive results will not be available for several years. 

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