However, the more depressed group became relatively larger in the CATIE-trial as a consequence of the lower cut-off (CDSS ≥ 6) for depression.
This contrasts with decreases in disease activity in placebo-treated patients usually seen in clinical trials as a consequence of the 'placebo effect'.
Severe RA patients with very high CRP treated with more than 5 mg prednisone are not influenced by steroids, but moderately active patients on more than 0 but ≤ 5 mg/day prednisone could be excluded from clinical trials as a consequence of lowered CRP.
It is unclear what drove the decreases in hs-CRP in the placebo group but it could be speculated that it was in part regression to the mean, and possibly related to increased compliance with background regimens that can also be seen in clinical trials as a consequence of closer follow-up.
Suboptimal drug concentrations, to those defined as optimal in clinical trials, can pertain as a consequence of the pharmacokinetics and pharmacodynamics of the drug mediated by host genetic background, adherence to recommended drug regimens and other factors such immune-incompetence and nutritional state of the host.
The results of any comparison methods (including direct comparison trials) may be biased as a consequence of bias in primary trials involved.
Dramatic problems, such as the sudden death of a young patient in a gene therapy trial, as a direct consequence of viral vector infusion 30, have driven researchers to improve the safety of the viral vectors, by reducing the immunogenicity of vector capsid proteins 31.
Also, methodologies of clinical trials have advanced significantly as a consequence of the introduction of CSIs.
In the sensitivity analyses, effect sizes were generally of comparable magnitude in both countries, although results in American trials consistently achieved statistical significance as a consequence of the larger sample sizes in these trials (Table 4).
The different results for verbal versus non-verbal trials may therefore be regarded as a consequence of the participants' coding strategies.
