Designing clinical trials for the treatment of delirium

A randomized controlled trial of quetiapine versus placebo in the treatment of delirium

“…Strict inclusion criteria, a high baseline score on the validated primary outcome measure, use of other validated measures, information from the case notes to supplement the patient and nursing staff interviews, homogeneity of subjects, use of a flexible dosing regimen, and frequent follow-up to 30 days are strengths in the methodology of this study. Indeed, a similar methodology has been recommended for designing clinical trials in this field [13].…”

Randomised control trials for delirium: Current evidence and statistical methods

“…For all of these reasons, some standard statistical tools may be less appropriate in delirium settings. It is, therefore, important to give statistical approaches for delirium trials a great deal of consideration [10,11]. Grover et al rightly used familiar statistical methods to compare in detail their randomised treatment groups at baseline, and demonstrated that randomisation had the desired effect of producing comparable groups.…”

“…Though it is certainly not the only possibility, we imputed the midway point between the patient's last observed DRS-R-98 and its mean at the time in question among those who actually completed the trial. Other examples of imputation in delirium are baseline observation carried forward (BOCF) and last observation carried forward (LOCF) [11]. However, these imputations do not typically capture the kind of trajectories seen in delirium trials, and tend to place unwarranted emphasis on end-of-trial comparisons.…”

Treating an Established Episode of Delirium in Palliative Care: Expert Opinion and Review of the Current Evidence Base With Recommendations for Future Development

“…This notion needs to be challenged in a well-designed placebo-controlled trial. 142 Because of a substantial number of participant study withdrawals (as a result of clinical deterioration or death) in palliative care populations, a palliative-modified intention-to-treat analysis should be considered in the evaluation of RCTs. 143 Drug therapy trials need to address dosing and titration regimens (including variations in regimens according to motor subtype), different routes of administration, and adverse events (including EPS), in addition to efficacy.…”