Product Classes And Resultant Clinical Trial Issues

Many of the principles outlined in other chapters for Phase I and II studies of these compounds are equally applicable to the testing of most biotechnology products. The same basic principal of demonstrating clinical tolerability as a priority over proving efficacy must apply. Other chapters also discuss some specific toxicology and drug discovery aspects of biotechnology products.

The design of a development program for a biological product has the same principles as for ordinary drugs, and this should be familiar to the competent clinical trialist. The development program should be determined by the nature and needs of the disease; often the pharmacological activity of a biological product is likely to be very precise, e.g. an antibody will bind to a previously identified, narrow range of antigens, and the pathogenesis or source of antigen presentation will have a fixed relationship to a well-described disease or set of diseases. Equally useful in the case of biologics is to begin development with an agreed, desirable package insert or product information leaflet. That document can then be used to define the development strategy. Only those tactics (i.e. clinical trial designs, milestones, and product-killing findings) that are justified or validated by that strategy should be implemented. The nature and seriousness of the disease being treated is just as important as in more orthodox clinical trials—the degree of lethality or morbidity associated with the disease treated with existing therapies is correlated positively with the degree of intolerability of the test agent that may be accepted.

Likewise, the trialist who switches to a biological product will find it very familiar to prove efficacy by comparing study medication to active or placebo comparative agents. With 'breakthrough' agents that offer the potential for a new type of therapy, clinical trials can be conducted, comparing the trial agent to a placebo. As usual, the central ethical consideration is whether standard treatment is being withheld from patient, and the debate should not be about the use of placebo in an absolute sense. Dose-response relationships need to be evaluated for biological agents prior to approval, even when the biological response is a 'all-or-nothing' type of response (e.g. serological conversion). It should be remembered that dose-response relationships must be understood for populations, as well as within individuals. Therapies like vaccines need to be evaluated in different racial populations.

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