Dr Michael Silverman of BioStrategics Consulting Ltd, reviews the type of clinical trial end points to use at different clinical development phases of a pharmaceutical product.
In my last blog I talked about the general concept of clinical trial end points, but I want to go a little deeper this time into a more specific example. Clearly the type of clinical trial end point one chooses for a particular clinical study depends very much on the phase of development and the goals of that study. As development progresses and more is learned about the product, how it works, in what patient groups, its safety profile, then
the end points chosen will change accordingly. To better understand this evolution, let us examine a hypothetical new drug for treating congestive heart failure (CHF).
Phase 1 Clinical Study Primary End Point: Safety
Most phase 1 studies are not conducted in people who have the disease in question (the exception being drugs with low therapeutic indices for use in life-threatening diseases such as cancer and AIDS). The end point for this first in human study is usually safety and is conducted in human volunteers. The safety outcomes are assessed after single and multiple dose administrations.
Phase 2 Clinical Study Primary End Point: Efficacy – Increase in cardiac output.
Phase 2 studies are usually exploratory studies in each candidate indication to determine which are most suitable for further development. In the case of CHF, the end point is efficacy as indicated by increased cardiac output measured by echocardiography. Phase 2 studies often explore the most appropriate dose of drug to use too, looking for the best efficacy without causing undue safety risks.
Phase 3 Clinical Study Primary End Point: Efficacy – Reduction in Mortality Rate
In the case of CHF, the end point used in Phase 2 studies will not suffice for a Phase 3 study as the FDA and the market place requires the demonstration of clinical relevance and benefit. Typically, the end point would be reduction in mortality rate and would therefore require the study to follow patients for a longer period of time.
Phase 4 Clinical Study Primary End Point: Efficacy – Market Driven
If the Phase 3 clinical study for reduction in mortality rate in CHF demonstrates the new drug is effective and it gains FDA approval, then Phase 4 studies can be used to expand the indications to capture more of the CHF market. For example, treatment of CHF in patients over the age of 65; use in combination with beta-adrenergic blockers to treat CHF; and the avoidance of hospitalization for exacerbations of CHF.
I would be delighted to hear your thoughts on these issues, your approaches, or anecdotes about decisions you have faced in similar circumstances. To make comments or ask questions, click on this link.
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