Everyone who is writing or reviewing a clinical trial protocol attempts to ensure that he or she considers all of the important aspects that should be included in a protocol. Every trial is very different in terms of the objectives, goals, details, and strategies involved; therefore, it is not possible to have a single approach or set of questions to use for assessing all protocols that will ensure the trial has considered every possible issue. The primary goal in posing a series of questions to use in reviewing or assessing your own or someone else’s protocol is to hopefully ensure that you have not overlooked important aspects that may require a protocol amendment while the trial is being conducted. Because it is extremely important not to overlook relevant details or issues, companies usually have teams of people discuss various aspects of each protocol, often at great length over a period of many weeks or even months, to determine what approach or wording to use. Some trials take many months of review and re-reviews to ensure that all aspects have been adequately addressed. Nonetheless, there is a core list of basic questions or issues that should be considered in most, if not all, clinical trials, and this chapter presents many of those core questions. There are literally dozens or even hundreds of questions that can be asked about most individual aspects of a trial, but if one limits oneself to considering the three to five most important questions on a specific topic, which ones will they be?

By identifying and then addressing these questions, as well as other questions that a company determines are of importance to its own investigational drugs or devices, it will help ensure that the protocol does not have serious flaws and that the company will not have to modify the protocol while it is being conducted. In other words, one can shorten the time for a product’s development by being assiduous in considering as many of these and other core questions prior to initiating a clinical trial.

The following questions deal with issues that go beyond the basic design and standard elements of a clinical trial that are found in standard textbooks (e.g., Guide to Clinical Trials). These do not represent a complete or even extensive list but are indicative of the types of broad questions that one can create and use for the purposes discussed if one is limited to three or so questions on any single category.