Placebo-controlled studies subject numbers

A number of studies have investigated the potential of melatonin to alleviate the symptoms of jet lag. Melatonin has been found to be effective in 11 placebo-controlled studies in reducing the subjective symptoms of jet lag such as sleepiness and impaired alertness (Arendt 2005). The most severe health effects of jet lag occur following eastbound flights, since this requires a phase advancement of the biological clock. In a recent study, phase advancement after melatonin administration (using 3 mg doses just before bedtime) occurred in all 11... 

Aerosol therapy with acetylcysteine can cause broncho-constriction. In 31 ambulant asthmatics using 10% acetylcysteine solution, there was a mean reduction of 55% in the FEVi in 19 subjects. The addition of 0.05% isoprena-hne reduced the number of patients who developed bronchoconstriction from 19 to 5 (SEDA-5,170). In two placebo-controlled studies, involving over 700 patients, there was no difference in adverse effects between oral acetylcysteine and a placebo. There was, however, no improvement in FEVi in these studies (3). 

As a result of these difficulties, only a few of the medications commonly employed for treatment of autism spectrum disorders (ASD) have been subjected to randomized, double-blind, placebo-controlled studies. Most published studies are uncontrolled, open-label studies of small numbers of patients. Because of the high incidence of response to placebo frequently observed in controlled studies of autism therapies (Aman et al., 2005 Sandler et al., 1999 Belsito et ah, 2001 Sandler, 2005), open-label studies are frequently misleading and are of little value for assessing treatment effectiveness, although they can be useful for identifying serious adverse effects. 

Another placebo-controlled study tested the effectiveness of ginger in preventing postoperative nausea and vomiting (Arfeen et al., 1995). This randomized, double-blind study included 108 subjects slated for elective gynecologic laparoscopy. The number of subjects provided 80% power to detect a reduction in the incidence of nausea from 30% to 20%. All patients received 10 mg of diazepam orally and were randomized to receive two 500 mg ginger capsules, one 500 mg ginger capsule and one placebo capsule, or two placebo capsules 1 h prior to surgery. Nausea, when present, was rated on a scale of 1 to 3 (mild,... 

In a randomised, placebo-controlled, study, 8 healthy subjects were given rifampicin 600 mg daily for 5 days and then on day 6 they were given a single 20-mg oral dose of zoipidem. It was found that the rifampicin reduced the zoipidem AUC by 73%, reduced the maximum plasma level by about 60% and reduced its half-life from 2.5 to 1.6 hours. A significant reduction in the effects of zoipidem was also seen, as measured by a number of psychomotor tests (digital symbol substitution, critical flicker fusion, subjective drowsiness, etc.). ... 

No important changes in the pharmacokinetics of paroxetine were seen when 12 healthy subjects given paroxetine 30 mg daily were also given diazepam 5 mg three times a day. Adverse events were not inereased by the combination. In another study it was foimd that paroxetine did not increase the impairment of a number of psychomotor tests eaused by oxazepam.In vitro studies using human liver mierosomal enzymes have shown that paroxetine is a relatively weak inhibitor of alprazolam metabolism mediated by the cytochrome P450 subfamily CYP3A. Furthermore, a randomised, placebo-controlled study in 22 healthy subjeets reported no evidence for a pharmacokinetic or pharmacological interaction between paroxetine and alprazolam. ... 

Pancreas Case reports and pharmacoepidemiological studies have provided evidence that statins may cause pancreatitis. However, data from the SHARP study, a placebo-controlled study of the effects of a combination of simvastatin and ezetimibe on cardiovascular events in patients with chronic kidney disease, showed a reduction in the number of cases of pancreatitis [75] [40 -]. Recent prospective cohort study with 1062 subjects of whom 92 were taking statins found severe pancreatitis was more common in the statin nonuser than statin user. Pancreatitis-related mortality was higher in the statin nonuser, and among patients who developed severe acute pancreatitis, statin users showed lower Ranson s and APACHE II scores and lower maximal CRP, suggesting that prior statin treatment reduced morbidity and mortality in acute pancreatitis [76]. 

ECASS-II was designed to test a lower dose of rt-PA (0.9 mg/kg) during the same 0-6-hours time period after stroke onset, using similar inclusion criteria as in ECASS-I. ° The primary endpoint was the proportion with a favorable outcome on the mRS scale (defined as a score of 0 or 1). There was no difference in this outcome between rt-PA-treated and placebo controls (40% vs. 37%, p = 0.28). A separate analysis of the 158 subjects enrolled within 3 hours of stroke onset also showed no difference in the proportion with a favorable outcome (42% vs. 38%, p = 0.63) this result, however, must be treated with caution because in ECASS-II there was a substantially lower number of patients treated within 3 hours of stroke onset, compared to the 1995 NINDS rt-PA study. Parenchymal hematoma on post-treatment CT was seen in 12% of rt-PA-treated and 3% of placebo patients (p < 0.001). The 90-day mortality rate was 11 % for the rt-PA group and 11 % for the placebo group (p = 0.54). Protocol violations were much less frequent in ECASS-II compared to ECASS-I (9% vs. 18%), probably because of standardized training in CT interpretation at the study sites. 

Reminiscent of the trend with laboratory studies, most (33 out of 43 cited above) uncontrolled clinical trials with either healthy volunteers or cardiovascular patients suggest that oral and intravenous NO donors at therapeutic doses acutely inhibit platelet activation in vivo (vide supra). Aside from their lack of long-term dosing and a placebo control group, several considerations restrict the predictive clinical value of these uncontrolled clinical studies limited numbers of subjects nonuniform criteria for subject entry and treatment outside of the trial induction of adrenaline or... 

Controlled and uncontrolled or open studies of the CCBs in affective illness are reviewed in Table 6-3. Initial open and blind studies of the phenyl-alkylamine L-type CCB verapamil were positive in the affective disorders, particularly in the treatment of acute mania. However, some preliminary controlled data are negative (Janicak et al. 1998) these data are highly subject to a type II error with the design used, the relatively small numbers of patients randomly selected for verapamil and placebo, and the associated relatively high placebo response rate in acute mania observed in many controlled studies... 

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