FDA’s Latest Guidance on Multiple Endpoints in Clinical Trials

Per International Conference on Harmonization?(ICH), description of the benefits and risks of the drug for a given medical condition should be made available very clear by sponsor, regulatory bodies and other stake holders. This is possible with structured framework of clinical trial objectives, design, conduct, analysis, and interpretation.

Most clinical trials happening in drug development are assessing multiple endpoints of the drug and to document the proficiency of the drug to favorably affect one or more disease characteristics. This arises concern as there is probability of false conclusion about drug’s effects with respect to numerous endpoints.

On requests and comments received from various pharma industry personnel, FDA finalized the guidance document with more detail on the differences between secondary and exploratory endpoints, as well as greater clarity on interpreting the endpoints in the primary and secondary endpoint families.

• When a single end point tested at two sided α = 0.05, the probability of finding a difference between the treatment group and a control group in favor of the treatment group when no difference exists in the population is 0.025 (a 2.5% chance).
• If there are two independent endpoints, each tested at two-sided α = 0.05, and if success on either endpoint by itself would lead to a conclusion of a drug effect, and so the probability of falsely finding a favorable effect on at least one endpoint is approximately 0.05 (5% chance).

As the number of endpoints or analyses increases, the Type I error rate ("There is always some possibility of mistakenly rejecting the null hypothesis when it is, in fact, true. Such an erroneous conclusion is Type I error rate”) can increase well beyond 2.5% due to multiplicity. There are many strategies and methods that can be used, as appropriate, as described in the guidance. Each of these methods has advantages and disadvantages, and the selection of suitable strategies and methods is a challenge that should be addressed at the study-planning stage. Statistical expertise should be enlisted to help choose the most appropriate approach. Failing to appropriately control the Type I error rate may increase the risk of a false positive conclusion; the guidance is intended to clarify when and how multiplicity due to multiple endpoints should be managed to avoid reaching such false conclusions.?

For more information on Type I, Type II, and Types of Multiple Endpoints, please visit https://www.fda.gov/media/162416/download.

Visit our website -?https://paradigmit.com/clinical-trial/?Or you can write us at?[email protected]??

Follow us for more -?https://www.dhirubhai.net/company/paradigmittechnologyservices/?viewAsMember=true??