Findings from Clinical Trials

Extensive tables of data will accompany the regulatory application so that the regulators can nm an independent analysis. In contrast, only limited data are published in journals. The editor and the reviewer, when provided with the scientific paper to be published, are seldom provided with adequate data to allow a detailed critique. For the manufacturer, the findings from clinical trials form the basis of what is said about the efficacy, safety and quality of a new medicine... 

Recent evidence from observational studies indicates that vitamin Bg status is highly likely to be associated with vascular diseases, albeit that the findings from clinical trials were inconsistent. 

Subsequently the medication was approved for self identified African Americans by the Federal Drug Administration (FDA), the first time a medication was approved for a specific racial group (US Food and Drug Administration, 2005). This combination was then marketed as BiDil. The approval led to a great deal of controversy and discussion, much of it critical, about the FDA decision. The findings from these trials, however, provide evidence that ethnicity can make a difference in clinical treatment response (Sankar 8c Kahn, 2005). 

One of the main reasons for excluding patients from clinical trials is to make it easier to find differences between the drug and the placebo.26 There are two ways in which excluding some patients from the trials can help accomplish this aim. One is to eliminate those who are most likely to respond to a placebo. To accomplish this goal, patients are excluded from clinical trials if they have only been depressed for a short time, if they are only mildly depressed or if they respond to placebo treatment during the placebo run-in phase. 

Data from repeat-dose toxicity studies are essential for CTAs in the early stages of development of a compound, but are superseded once there is a reasonable amount of human data. Any target organs that are identified in the toxicity studies should be monitored in clinical trials. Definitive data on the effects derived from clinical trials will show whether the animal studies are predictive of the effects in humans. This information can then be used to help interpret findings in reproductive toxicity studies, such as whether general toxicity in the adult is relevant. If adult toxicity in animals is deemed relevant, the exposure at which it occurs can be used to estimate the clinical relevance of any reproductive effects. If toxic effects in animals are induced at exposures greatly in excess of the clinical exposure, then they might not be clinically relevant. 

The atypical antipsychotics are still relatively new, particularly some members. Information about new drugs is first available from clinical trials and then modified by observations from clinical practice, and the atypical antipsychotics are no exception to this pattern. Some findings from clinical practice have already confirmed those from clinical trials for the three marketed atypical antipsychotics (i.e., risperidone, olanzapine, and quetiapine) and are generally applicable to choosing an atypical antipsychotic for patients with a wide variety of psychotic disorders, although least is known about ziprasidone, the newest member of this group. 

Clinical and angiographic results of the most important of these studies are described in Table 2. As we can see in the table, although there were some differences in the design of these studies, there were correlative findings from those trials, in terms of angiographic follow-up results and safety long-term outcome data. 

Results from many of these studies have been described in detail in a recent review [168] key findings from these trials are grouped below by indication. In addition, several more preliminary studies examining novel indications are mentioned. The major named clinical trials with the more advanced fibrinogen antagonists are summarised in Table 2.8. 

The NCI has a policy for inclusion of women and minorities to ensure that research findings can be applicable to all those at risk of the disease. Women have historically been excluded from clinical trials. Emerging information shows that dosing and toxicity may differ in men and women [25]. In addition, recent data suggest that molecular markers may have differential implications based on gender. For example, observed polymorphisms in the EGFR have opposite effects on overall prognosis in men and women [26]. 

Name and description of the investigational product(s). A summary of findings from non-clinical sfudies and from clinioal trials that is relevant to the trial. Summary of the known and potential risks and benefits, if any, to human subjects. Description of and justification for the route of administration, dosage, dosage regimen, and treatment period(s). A statement that the trial will be conducted in compliance with the protocol, GCP and the applicable regulatory requirement(s). Description of the population to be studied. References to literature and data that are relevant to the trial, and that provide background for the trial... 

Only two randomized, controlled trials have been completed, and neither provides anything like compelling data (Table 2.6). Chouinard and Albright (1997) conducted a unique evaluation of a subset of patients from a previously conducted clinical trial. Subjects were categorized and profiled at baseline and end point according to clinical severity, and a group of psychiatric nurses were asked to rate various aspects of likely outcome and quality of life to each profile (mild, moderate or severe symptoms). Health state utilities were then calculated risperidone was found to provide more than double the number of quality-adjusted life years compared with haloperidol. Csernansky and Okamoto (1999) conducted a rather more conventional trial, but included no economic analyses. However, they did find that the use of risperidone substantially reduced relapse rates compared with haloperidol—an outcome likely to have a positive impact on cost-effectiveness. 

Recent findings from the ATBC stndy even showed that P-carotene snpple-mentation increased the post-trial risk of a hrst-ever non-fatal MI. Two secondary prevention trials, the Heart Protection Stndy and the ATBC presented similar resnlts. The former showed no association between P-carotene and fatal or non-fatal vascular events and the latter reported signihcantly increased risks of fatal coronary events in the P-carotene-snpplemented gronp. Resnlts of clinical trials focused on the effects of carotenoids on CVD biomarkers are controversial. Although carotenoid supplementation increased sernm levels,only lycopene was shown to be inversely associated with lipid, protein, DNA and LDL oxidation, and plasma cholesterol levels. - - ... 

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