Clinical trials power

Kraiczi, H., Frisen, M. Effect of uncertainty about population parameters on pharmacodynamics-based prediction of clinical trial power. Contemp Clin Trials 2005, 26 118-130. 

Out of the numerous compounds these investigators made, they eventually selected /S-hydroxyethyla oquinine for clinical trial owing to its low toxicity, relatively high bacteriostatic power and lack of deleterious side-effects. The following table summarises the data available on these two points for this drug and its near relatives. The name opocupreine is used by Cretcher for opoquinine (p. 452). 

The number of partidpants must be chosen so that the trial wUl have suflEdent statistical power , particularly in the case of confirmatory trials. As a general prindple, the greater the number of data, the greater the confidence there is in demonstrating that a statistical difierence between two groups exists, or not. However, numbers of participants will be constrained by cost considerations, the availability of suitable subjects and, above all, by the ethical prindple that subjects should not be enrolled in clinical trial unless they add scientific value. 

There are reports of the benefits of botulinum toxin in the treatment of cerebral palsy in children. The toxin, produced by Clostridium botulinum, is a powerful and deadly poison, but is also an effective muscle relaxant. It is not licensed for use as such in the UK but is undergoing clinical trials. Current evidence suggests that repeat injections are necessary some 4-6 months after the first. 

Statistical methods are often employed to determine the study sample size and optimize power. Outlining the methods for calculating sample size and power for clinical trials is beyond the scope of this chapter. Interested readers are referred to texts by Chow and Liu (1998), Hulley and Cummings (1988), and Shuster (1990) for specific information on sample size and power estimation methods. 

Clinical trials are costly to conduct, and results are often critical to the commercial viability of a phytochemical product. Seemingly minor decisions, such as which measurement tool to use or a single entry criterion, can produce thousands of dollars in additional costs. Likewise, a great deal of time, effort and money can be saved by having experts review the study protocol to provide feedback regarding ways to improve efficiency, reduce subject burden and insure that the objectives are being met in the most scientifically sound and cost-effective manner possible. In particular, I recommend that an expert statistician is consulted regarding sample size and power and that the assumptions used in these calculations are reviewed carefully with one or more clinicians. It is not uncommon to see two studies with very similar objectives, which vary by two-fold in the number of subjects under study. Often this can be explained by differences in the assumptions employed in the sample size calculations. 

The optimal myeloablative preparative regimen is challenging to study because several indications for HCT (e.g., SCID and thalassemia) are rare enough that it is not feasible or is cost-prohibitive to conduct clinical trials that are powered adequately to detect clinically relevant differences. The longterm outcomes of busulfan-cyclophosphamide (BU-CY) and... 

Operational Data Model (ODM). The ODM is a powerful XML-based data model that allows for XMF-based transmission of any data involved in the conduct of clinical trials. SAS has provided support for importing and exporting ODM files via the CDISC procedure and the XML LIBNAME engine. 

SAS has always had and will maintain a central role in the data management, analysis, and reporting of clinical trial data. Because of the strong suite of SAS statistical procedures and the power of Base SAS programming, SAS remains a favorite of statisticians for the analysis of clinical trial data. Several companies have built their clinical trial data management and statistical analysis systems entirely with SAS software. More recently, SAS has offered SAS Drug Development as an industry solution that provides a comprehensive clinical trial analysis and reporting environment compliant with 21 CRF-Part 11. 

Some software applications that you may use for reporting clinical trial information have their own scripting languages. For Microsoft Office applications you can write powerful local utility functions with Visual Basic or VBScript. Other applications, such as Adobe Acrobat, may use JavaScript for utility functions. 

The African-American Heart Failure Trial showed that a large number of African Americans can be recruited in sufficient numbers with enough power to show efficacy in a clinical trial. In psychiatry the large START) study of depression was made up of 24% minorities (Trivedi etal, 2006). The recently completed Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) was able to recruit enough African Americans to make up about one third of its participants (Stroup et al, 2006). 

Despite the weakness of the data, the idea that iproniazid and imipramine were effective antidepressants came to be widely accepted. This is not really surprising, in the context of the times. In the 1950s and 1960s, the power of the placebo effect was just beginning to be recognized, and placebo-controlled clinical trials were rare. New treatments were often accepted on the basis of clinical experience and the testimony of experts in the field. 

The placebo effect also depends on what people are told about the treatment they are given. The effect is smaller when patients are told that their treatment might be a placebo, as is routinely done in clinical trials, and is larger when people are told that their treatment has been shown to be powerful.17 Because the placebo effect can vary so much, attempts to estimate its power in general, without specifying the condition being treated and the conditions under which the placebo was administered, are meaningless. 

If the placebo effect in depression is so powerful, perhaps we should just prescribe inert placebos to depressed patients. They have been tested in thousands of clinical trials, they are the standard against which all other medications are evaluated, and they are safe enough to be taken by pregnant women, small children,... 

Recently, BN 52063 has been demonstrated to be effective against mastocytosis [304], a condition which was previously incurable. This suggests that PAF, as well as mast cell degranulation, may have a role in systemic mastocytosis. The injectable (pure) form of BN 52021 is much more powerful than BN 52063. Preliminary clinical investigations have shown a long and intense inhibition of ex vivo PAF-induced platelet aggregation. The injectable form is now under clinical trials in graft rejection, stroke, haemodialysis and shock. 

Most clinical laboratories have established a standard battery of tests that includes most or all of the basic parameters listed in Table 20.12. If a dipstick is used to test the urine for several parameters, it is useful to use one that measures occult blood, even if a microscopic examination will count the number of red blood cells per high-power field. The means of obtaining the specimen should be indicated (i.e., normal voiding sample, clean catch, midstream, catheterization, suprapubic tap, or cytoscopy), especially in clinical trials in which an antidiuretic or antibiotic (or other relevant drug) is being tested. 

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