Letter from the Editors: Clinical Trials in Nuclear Medicine
Article Outline
Nuclear medicine is one of the areas of medicine that is particularly dependent on basic science. Chemistry, radiochemistry and physics, as well as physiology and biochemistry, are essential ingredients to understand and generate the images that we review. Regardless of this strong basic science component, when we begin to interpret the meaning of the images we see, nuclear medicine becomes as much a part of the “art of medicine” as any other specialty. A very significant component of medical practice is based on clinical experience. Decisions about diagnosis, treatment, and interpretation of images are strongly influenced by the “experience” of the practitioner and his or her intuitive sense of the meaning of the observation and the patient's complaint. This classic “practice of medicine” is no longer acceptable in the 21st century. There is an increasing trend towards “evidence-based” medicine. Third parties that review payment for services rendered and, in the case of nuclear medicine, that approve or disapprove procedures for routine clinical use, are increasingly demanding more strict measures of accuracy, sensitivity and specificity. This journal was one of the first to recognize the importance of this requirement. Acting on the advice and suggestions of Dennis Patton (1930-2007) in 1978 we published an issue devoted to “Decision Making in Clinical Nuclear Medicine” (Dennis D. Patton, MD, Guest Editor, October 1978, pages 271-365). This was one of the earliest publications in clinical medicine devoted to what has now become a routine requirement for the analysis of studies that are performed to shape medical practice. Dennis put together a comprehensive and highly informative seminar that even today has great impact. He wrote an incisive editorial for that issue and the lead article which was entitled “Introduction to Clinical Decision Making.” The editors believe that this is such an important seminal article in this field that we have reprinted his original contribution in this issue where its relevance remains.1 In 1993 we revisited this subject from a somewhat different point of view in an issue entitled “Socioeconomic Issues in Nuclear Medicine.” Dennis Patton once again provided a seminal contribution on cost-effectiveness in nuclear medicine. In that contribution he made the statement “much work remains to be done in forming a coherent consistent procedure for assessing cost-effectiveness in nuclear medicine.” Here we are 17 years later and we have made some progress, but much work remains to be done.
A critical basis of acquiring the information needed to make these assessments is the clinical trial. The editors have decided to devote this issue of Seminars to clinical trials in nuclear medicine because this has come to play a vital role in the way we practice and in how we are allowed to practice. The great importance of the clinical trial in nuclear medicine today is emphasized by the creation of the Clinical Trials Council of the Society of Nuclear Medicine, which has recognized this important approach to evaluating our work. Dr. Michael Graham has outlined for us clearly the basis of and the structure of the Clinical Trials Council.2
Although this is not a subject that most of us encountered in medical school, we cannot practice without a full understanding of the components of the clinical trial. Drs. David Rollo, Sanjay Machado, and Mauro Ceschin describe here the concepts that go into the formulation, design, and performance of a clinical trial.3 The clinical trial frequently requires some type of coordinating center, which Drs. John Seibyl, Kenneth Marek, and I. George Zubal explain based on their wide experience in this area.4 Few clinical trials are conducted as a single-center effort, since the number of patients needed to achieve statistical significance is usually more than can be recruited in one clinical center. Thus, the need for a careful and well thought out design and the need for a clinical trial coordinating center to be sure that the data from all of the centers are analyzed in the same way and are compatible, in order to lead to an accurate analysis of the results. In the case of nuclear medicine trials, there usually is a radiopharmaceutical component. Here too, uniformity and conformity among centers and among various pharmaceuticals used are essential to the success of the trial. Jeffrey Norenberg, Neil A. Petry, and Sally Schwarz outline for us the operation of a central radiopharmacy.5
After the trial has been designed, the patients recruited, and the coordinating center has analyzed the data utilizing the radiopharmaceutical that is being tested or the machine that is being tested, the data must be analyzed. The basic statistical concepts that go into the analysis of the trial data are clearly and succinctly analyzed by Drs. Sylvia Wassertheil-Smoller and Mimi Kim.6
Two major regulatory components of the trial are the Food and Drug Administration (FDA) and the Institutional Review Board (IRB). The FDA has very well-defined rules for testing and approval of new radiopharmaceuticals, which must be adhered to by the company or the individual that is proposing a new agent. New instrumentation similarly has well-defined guidelines. Dr. Ravi S. Harapanhalli has provided us with a detailed description of these processes based on his experience as a former branch chief in the office of new drug quality assessment of the FDA.7
Finally, there remains the question of oversight. Before a study can be commenced, it must be shown that it will do no harm and that there is a potential benefit to either the individual participating in the study or to the population at large. The study must be monitored by an objective third party for unexpected, untoward events which might require early cessation of the study, and for accuracy in the collection of data, as well as to insure the patient's right to informed consent. Raffaella Hart and Michael Belotto outline for us the functions of the IRB, which serves in this role.8
Overall, the conduct of a clinical trial is a highly complex process involving many components. Much more is involved than the trial itself, since somewhere in the very beginning someone has to conceive of the product that is going to be tested. In order for the practicing nuclear medicine physician to review the literature, understand its significance, and evaluate any new or existing procedure that is being discussed, it is necessary for him or her to be fully familiar with all of these components that are part of the final product.
We decided to devote this issue of the Seminars to the clinical trial to provide the reader with an up-to-date analysis of how our various radiopharmaceuticals come to market. For most of us this has been an on-the-job learning experience with little if any exposure in medical school. We hope that this issue will help to fill those gaps in the nuclear medicine physician's knowledge that are critical to the determination of how they conduct or modify their practice.
References
- . Introduction to clinical decision making. Semin Nucl Med. 2010;40:319–326
- . The Clinical Trials Network of the Society of Nuclear Medicine. Semin Nucl Med. 2010;40:327–331
- . Design of clinical trials. Semin Nucl Med. 2010;40:332–337
- . The role of the core imaging laboratory in multicenter trials. Semin Nucl Med. 2010;40:338–346
- . Operation of a radiopharmacy for a clinical trial. Semin Nucl Med. 2010;40:347–356
- . Statistical analysis of clinical trials. Semin Nucl Med. 2010;40:357–363
- . FDA requirements for testing and approval of new radiopharmaceuticals. Semin Nucl Med. 2010;40:364–384
- . The Institutional Review Board. Semin Nucl Med. 2010;40:385–392
PII: S0001-2998(10)00048-6
doi:10.1053/j.semnuclmed.2010.06.001
© 2010 Elsevier Inc. All rights reserved.
