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XIII. Pharmaceutical Structure |
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The structure of the group working on drug development is most important. Individuals that have familiarity with their field are requisite. Pharmacologists, pharmacokineticists, those with expertise in trial design, and individuals with strong preclinical study knowledge all are necessary components. Occasionally one or two individuals have the expertise, but often a team is needed to pursue the objective. At least an advisory group with broad expertise should be interposed in the development process to take a number of areas into consideration early in the planning stages. With an adequate structure, the resources must also be available. One cannot be ahead of the preclinical development program and make rational decisions. One needs the appropriate technology, but one also needs to coordinate resources in manufacturing (including placebos and positive controls) with packaging and regulatory considerations. Marketing needs to be involved. Developing a drug for supraventricular arrhythmias when the treatment of all arrhythmias is the goal of the company can be a disaster. While for medical reasons some groups will be excluded in SVT development, excluding groups with very severe LV dysfunction and ventricular arrhythmias from a general antiarrhythmic development program would not be acceptable. The capabilities of the compound must be assessed by the development group and fitted in with the corporate goals for that drug development of that compound. Then a rational drug development plan can be devised. |
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XIV. Dose and Serum Concentration Measurements |
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Perhaps the most fundamental issue in drug development is establishing the dose for a study. This is indeed a difficult area and one that is inadequately handled in many instances. It would be safe to say that perhaps 75% to 95% of all drugs are being employed at doses that are not optimum. Dose ranging is difficult, expensive, and time consuming, but so very important. Finding a minimally effective dose can help in reducing adverse side effects of agents and can be an important step in an effective drug development program. For years, the dose of the thiazide diuretics were perhaps 50 times the needed dose for antihypertensive therapy. This is both bad for drug development and bad for the patient taking the medication. We can do better than this, and more and more studies, due to FDA insistence, more often than not, are rather elegantly determining the effective dose range. It is also important to state that an effective dose range for one individual may not be an effective dose for another individual. Differences may not just be on an individual basis, but may vary within special populations. In fact, it is rather important to try to look at a more homogeneous population early on, and exclude the special popu- |
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