Clinical studies, drug guidelines

Several specialized reviews on detection of QT liability in the clinical development phase have already been published and the reader is referred to these publications [63]. Guidelines of the International Society for Holter and Noninvasive Electrocardiology (IS H N E) for electrocardiographic evaluation of drug-related QT prolongation are also available [161]. The main issues related to measurement of the QT interval in clinical studies are summarized in Table 3.4. An important aspect is the calculation of sample size usually 40-60 subjects per treatment arm are required, implying high cost [162-164]. 

Guidelines for General Pharmacology Studies — Japanese Guidelines for Non-clinical Studies of Drugs manual 1995... 

Anon., Guidelines for general pharmacology studies-Japanese guidelines for non-clinical studies of drugs manual 1995 (pp. 71-80), Eds., Nippo Yakuji, Ltd. 

The period in the drug development process at which results of these studies are required varies somewhat from country to country, but recommendations are made in the ICH guidelines. In most instances, Stage B studies are required prior to phase 2 clinical studies, the Stage A study is required prior to phase 3, and the Stage C study is needed for the NDA. Circumstances for an individual drug or requirements of certain countries may warrant a modification of this schedule. 

There should be consistency between the possible adverse events described for the study drug in the protocol, investigator s brochure and ICF. Most coimtries have specific requirements for their ICF. It is essential that the requirements are known when the country-specific ICF is prepared. These examples could easily have changed by the time the reader is checking an ICF. In the United Kingdom, reference should be made to the ABPI (Association of the British Pharmaceutical Industry) Clinical Trial Compensation Guidelines. In other countries, for example, Ireland, the study subject is allowed a specific length of time to decide whether to enter the study. 

The prevention of cardiac events is the first priority. When there is a choice between two methods for effectively relieving the patient s symptoms, you have to choose the one for which there is proof or at least a high possibility for these events to be prevented. Because MI can be critical, non-pharmacological therapy might have a higher priority but the above mentioned principles for therapy selection is also effective for the choice of drugs. There is a need to keep updated with respect to treatment guidelines and the latest clinical studies. 

Japanese Guidelines for Non-Clinical Studies of Drugs Manual 1995. Yakuji Nippo Tokyo, 1995... 

The overview should reference any specific FDA guidelines used and any FDA-sponsor discussions held on major issues, such as an end-of-phase 2 conference. The critical features of the trials should be explained, including duration, study design, and particular advantages or potential problems examined. If there is pertinent clinical literature (controlled or uncontrolled clinical studies or reports on patients), a review may be helpful. (The sponsor may want to comment on literature pertaining to closely related drugs that provide insight into potential problems or areas of special interest.)... 

An applicant may provide an overall summary of data from controlled studies. This section is optional and many firms do not include it because the results of the studies are presented in the integrated summaries of efficacy and safety, which will be discussed later in this chapter. The Guidelines for the Clinical and Statistical Sections of a New Drug Application also address the format and content of an integrated clinical/statistical report for a clinical study this too will be discussed later. 

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