Study design blinding

Appropriate study design should be selected to achieve the desired outcome. A description of the type/design of frial to be conducted (e.g., double-blind, placebo-controlled, parallel design) and a schematic diagram of trial design. 

Study Design Treatment, randomized, double-blind, placebo control, parallel assignment, efficacy study... 

The parallel-group, double-blind, placebo-controlled study design represents the golden standard of acute treatment trials of depression, mania and anxiety disorders. This design is intended to limit bias, in particular selection and measurement bias. Trials based on this design are expected to provide information about the effect size of a new compound and its side-effect profile. 

Several features should be considered when classifying study designs by their quality. Although our classification is arbitrary, it is intended as a device to focus on all of the important criteria, not just one (e.g., blinding ). 

Arvanitis and Miller (129) reported a multiple fixed-dose, placebo-controlled, double-blind study of quetiapine in comparison with haloperidol and placebo in acutely exacerbated patients with chronic schizophrenia. Quetiapine was administered in five doses 75, 150, 300, 600, and 750 mg/day haloperidol was given at 12 mg/day. The study design had slightly more than 50 patients in each group. The 75-mg dose of quetiapine was clearly less efficacious than the higher doses. Doses of 150 to 750 mg/day were superior to placebo and comparable with haloperidol in reducing positive symptoms and 300 mg/day was superior to placebo and comparable with haloperidol for negative symptoms. 

Inflammation is an important factor in the development of cardiovascular disease. Most clinical studies involving inflammation parameters have been relatively small. The Nurses Health Study involving 727 women was the largest study designed to determine the effects of n-3 fatty acids on biomarkers of inflammation and endothelium activation (Lopez-Garcia et al., 2004). They found an inverse association between ALA intake and plasma concentrations of C-reactive protein (a marker for inflammation), Interlukin-6, and E-selectin. Bemelmans et al. (2004) also found an inverse association between C-reactive protein and ALA intake in a randomized, double-blind placebo-controlled study involving 103 hypercholesterolemic subjects. 

CAPRIE (52) was a randomized, blinded, international study designed to assess the relative efficacy of clopidogrel... 

A tabular presentation of studies by protocol, investigator, study design (e.g., randomized, double-blind, open, parallel, crossover), drug or other treatment used for comparison (if any), number of subjects (or patients, if used),... 

Controlled trials can be conducted under matched pairs, parallel, crossover, group comparisons, or mixed design conditions. Parallel and crossover study designs each have advantages and disadvantages. Both can be used to compare two or more treatments, one of which may be placebo. In a crossover study, all treatments to be compared are administered to every enrolled patient in a carefully designed and blinded sequence with an interim drug washout period. Each patient receives all treatments and thus serves as his or her own control. 

In addition to being accurate and valid, clinical findings must also be relevant to the anticipated therapeutic effect. They must be sufficient to prove that the efficacy of the study drug is comparable to, or perhaps greater than, a well-chosen and well-blinded control, and that its safety has been similarly profiled. Obviously, if the study design and protocol, including such basics as the study sample size, are not adequate for this complex task, the data collection... 

The statistician should note when interpreting the statistical analysis that the failure to find significant differences in the final data might be attributable to the quality of that data as recorded, perhaps to the quality of the study design or to insufficient sample size, therefore insufficient statistical power. Bias in clinical findings, particularly in nonblinded or poorly blinded studies, is one possible cause. 

Locally conducted trials are desired. These are conducted at a minimum of three general hospitals selected by the Ministry of Health and Welfare (MOHW) (A minimum of 90 patients is required. Study design may be open, double blind or comparative.). 

Study Design Randomized, double-blinded/single blinded Retrospective, case-control, etc. 

Cross-sectional studies can identify prevalence rates based on the distribution of a particular syndrome or malformation, but the study design makes it difficult to identify cause and effect relationships. Case-control protocols match the affected pregnancy to an unaffected pregnancy but, again, it is difficult to account for maternal recall bias and perhaps equally difficult to control for bias (even unconscious) on the part of the investigator. Cohort smdies, while suffering from problems of dose determination, are usually prospective, the largest, the most expensive, the slowest, and usually the most statistically powerful to detect reliable associations. Double-blind intervention studies, like those conducted with folic acid and prevention of NTD, usually yield the most conclusive data. 

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