Principles and Practice of Clinical Research

PRINCIPLES AND PRACTICE OF CLINICAL RESEARCH, 2nd ed., contains 29 chapters and is 430 pages long. Each chapter is by a different author(s). Surprisingly, only the introductory chapter is authored by one of the two editors of the book. The book is of moderate size. It too long to be called, "Clinical Studies in a Nutshell," and too short to be used as a resource for experienced clinical study monitors when they need expert advice. Chapter 6, entitled Data and Safety Monitoring Boards, is by Lawrence Friedman. This chapter is first rate. We learn several reasons why clinical trials have a Data Monitoring Committee (DMC). One reasons is that trials are double blinded and the investigator must also remain blinded. The DMC is the party to view the unblinded data. Second, where trials are held at multiple centers this makes monitoring by a single investigator difficult. The DMC is the party to monitor the multiple sites. Third, to avoid undue bias for wanting to halt a trial, or wanting to prolong a trial, a DMC is useful. Fourth, to ensure that any changes to a protocol that are made are made by an investigator that is kept unaware of the direction that the data are trending. Dr.Friedman provides some concrete, real-life examples of what a DMC can recommend. First, the DMC can suggest to drop a subgroup from the trial, for example, a subgroup that is found to do worse than the group receiving the standard of care. Second, the DMC can recommend sending a letter to all subjects warning them of a newly discovered adverse event, or even recommend that a new informed consent form be prepared and signed by all subjects. Third, the DMC can recommend that a trial be stopped early because of efficacy of the study drug (this is good news). Fourth, the DMC can recommend that a trial be halted for futility, that is, for failure to work, or for too many adverse events. Chapter 7, "Data Management in Clinical Trials," discloses the nuts and bolts of any clinical trial. We learn about the site initiation visit, where the sponsor manages eligibility criteria, randomization, blinding, study procedures, study agent administration, adverse event (AE) recording, and the Case Report Form (CRF) and data entry. In this practical chapter, we also learn about Serious Adverse Events (SAEs), and that they include life threatening events, events that cause or prolong hospitalization, events that cause persistent or significant disability, and birth defects. Regarding SAEs, we also learn that the investigator must report SAEs to the FDA and to the sponsor, and that the sponsor must provide FDA and all investigators with an IND Safety Report. Chapter 7 provides sample forms and sample tables, e.g., inclusion criteria, registration form, and a randomization form. The strong point of Chapter 7 is that it provides examples of actual forms that are filled out. Chapter 7 is too short. This important chapter could easily be 2 or 3 times as long. Chapter 8 b

It's a good collation on the practice of clinical research. Great learning examples to move forward.