Although the effectiveness of therapeutic apheresis may be established from uncontrolled trials, well-designed, randomized controlled trials provide the best evidence for a clinical benefit because this type of trial design minimizes bias.
However, because of the lack of published data in the literature regarding specified metabolic outcome measures at the time of trial design (2004 2005), and because of the exploratory nature of the substudy, no power calculations were performed for the substudy measures.
A total of 120 papers were excluded because of publication type (reviews or reports) or because of improper trial design.
However, this evidence has been inconclusive, because of observational trial design, small sample sizes, and lack of reproducibility in different patient populations [ 32, 33].
The epidemiological studies previously carried on the prevalence of PD in population exposed to environmental factors have produced controversial results, probably because of different trial design and different analysis methods.
Again, there was marked heterogeneity because of dissimilar trial design, the heightened risk for major bleeding complication was attenuated after excluding the study on ACS (OR 1.03; 95% CI 0.90 to 1.19; p=0.638).
Additional limitations include the fact that individual drugs cannot be evaluated because of the trial design, which assigned patients to a mechanistic treatment strategy rather than a specific drug, and the lack of a standardized claudication questionnaire, which might have resulted in the diagnosis of a few more PAD cases during follow-up.
Even if a unit has previously carried out a trial on the same condition the required information may not be to hand because of variations in trial design because of advances in knowledge and variations in eligibility criteria.
Results from clinical trials cannot be generalized to an entire disease population because of restrictions in trial design such as patient eligibility criteria and the type of patients willing to enter a study.
