Placebo use

A Phase II study was recently completed whereby Org-25935 was compared against placebo for the ability to improve negative symptoms in 246 subjects maintained on a stable dose of an atypical antipsychotic (data not disclosed) [46]. A second Phase II study in progress (200 patients) is designed to assess the efficacy of Org-25935 as a stand-alone therapy versus placebo, using olanzapine as the active control [46]. Org-25935 is also being investigated in separate Phase II studies as a treatment for panic disorder and for recidivism in subjects with alcohol dependence [46]. 

Non-inferiority trials are becoming more and more common as time goes on. This in part is due to the constraints imposed by the revised Helsinki Declaration (2004) and the increasing concern in some circles regarding the ethics of placebo use. These trials however require very careful design and conduct and we will discuss this whole area in a subsequent chapter. 

We only focused on studies complying with WHO (World Health Organization) [3] standards, i.e. performed double-blind versus placebo, using only the sublingual route with mite extracts. 

In a comparison of the initial and 5-day steady-state effects of loratadine, diphenhydramine, and placebo, using a number of psychometric tests, there was no detectable effect of loratadine compared with placebo, whereas diphenhydramine clearly reduced performance (70). 

When queried about adverse reactions, Heinzler stated that he had not paid them any particular attention, and could not recall any complaints. The judge then asked a series of questions about a 1956 publication in which Heinzler described his research findings. In particular, the judge noted that the publication described placebo use and precise testing methods. Heinzler, however, could not verify that the procedures he himself endorsed had actually been followed, stating simply that I did not see any side effects of a serious nature in the stationary patients, and other than some constipation, I simply did not observe anything. 53... 

The second study was a double-blinded comparative trial of secondary prophylaxis comparing 60 mg aerosolized pentamidine given every 2 wk after five weekly loading bases to placebo using a handheld FisoNeb ultrasonic nebulizer with a 5- xm MMAD particle size [36,37], The study was intended to run 6 mo, but it was terminated early, with a mean follow-up of only 3.7 mo. Aerosolized pentamidine significantly reduced the reoccurrence rate of PCP as compared to controls in this study [37,38]. 

This question has been debated in the medical literature i p since the 19th century. Arguments for placebo use have focused on the positive effects noted in clinical... 

A pharmaceutical or other product (which may be a placebo) used as a reference in a clinical trial. 

It is commonly stated that the analysis of extreme values often plays a more important role than that of the average values in clinical trials because it provides more information on the extent of safety concern at the individual level (14). Extreme values can be examined by creating frequency distributions for maximum absolute values as well as maximum increases from baseline (correcting for placebo), using reference limits of 450 and 500 ms on QT or 30 and 60 ms on AAQTc. It is important to account for covariates known to affect the distribution of QT/QTc values... 

Although it is certainly true that a valid comparison can be made of the effect of verum compared to placebo using t whether there are 25 patients in the one group and 75 in the other or 40 60 or 50 50 or, indeed, any such split except 0 100 or 100 0 (for which no estimate would be possible), the information given by such comparisons is not identical in every case. This is recognized by the variance of t, which is in fact proportional to the sum of the reciprocals of the two sample sizes thus, if the split is 25 75, the variance is proportional to 1/25 + 1/75 = 0.053. On the other hand, if the split is 50 50, then the variance is proportional to 1/50+ 1/50 = 0.04. This shows the value of balance. The variance is lower in the balanced case, but nobody denies that the comparison would be valid in either case. 

To simplify things, consider a meta-analysis of a series of trials that are of two sorts, those comparing rofecoxib with naproxen and those comparing rofecoxib with placebo. These have the structure of an incomplete blocks design. If a model is fitted with trial as a factor and treatments as another factor at three levels - rofecoxib, naproxen, placebo -it is actually the rofecoxib results that permit the comparison of naproxen and placebo. To try to use this comparison to justify pooling placebo and naproxen is a hopelessly circular argument. To the extent that the model above is used, all that will happen is that rofecoxib will be separately compared with placebo using those trials in which they appeared. 

As we have seen above, designs are possible in which there are more sequences than treatments. It is also not necessary for the number of periods to equal the number of treatments. For example, in a trial comparing two treatments we might decide to use four periods and two sequences as follows ABBA/BAAB. Here, each patient would receive each treatment for two periods. In a so-called incomplete blocks design we might have more treatments than periods. For example, we could have compared the doses of diclofenac to placebo using the sequences... 

Postsurgical Adhesion Data at One Week with HA/Interleuken-4 (IL-4) Formulations and Placebos Using Sidewall Model with Silk Sutures... 

The efficacy is proved in human tests involving a sufficiently high number of patients taking quite a long time, so that there could be no doubt about the results. Not only is a placebo used as comparison (— 3.6), but other known similar medicines... 

A NlRSystems Model 6500 was employed in the analysis with a ceramic disk used as the reference. Second-derivative spectra were used in the data analysis. The identification and classification algorithms used were supplied by the instrument vendor. In the first configuration, all but the 2% tablets were easily classified. The 2% tablets were not be differentiated from the placebo. Using the second and third configurations, only the 10 and 20%, placebo and clinical comparator tablets could be properly classified. 

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