Making clinical trials safer for human subjects.

I. CLINICAL TRIALS The pace of medical innovation is quickening, pushed by advances in biotechnology and pulled by growing demand for healthcare. Completion of the Human Genome Project has provided a multitude of data for determining genes and their functions, and stimulated the application of information technology and private capital for the development of new individualized drugs, gene therapies, and biomaterials for tissue and organ regeneration.1 Concurrently, demand for healthcare continues to grow, expanding the market for medical innovations that are proven in clinical trials to be safe and effective.2 Clinical trials, in which new biotech and other medical products are tested on human subjects, provide much of the data used by the federal Food and Drug Administration (FDA) to determine whether the products are suitable for routine use in healthcare.3 Thus, the trials are of obvious importance to medical progress and improvement of public health, and to those who have career and financial interests at stake.4 But clinical trials are also important to the human subjects involved because the products being tested on them may remedy their illnesses, but may also pose risks since the products have usually not been previously tested on humans.5 The clinical trial is "a point at which research and the practice of medicine intersect"6 because it is supposed to be designed and managed to achieve dual societal objectives: the generation of clinical evidence regarding the efficacy and safety of new products, information needed by the FDA to determine whether the products should be sold for medical use, and the responsible application of such products to selected human subjects for potential therapeutic benefit.7 In some respects, the clinical trial resembles the test procedures for introducing other new technologies into society. For example, the introduction of a new pesticide, aircraft, chemical manufacturing process, or method of producing energy, requires carefully designed field tests to discern gains, risks, and the adjustments needed to secure regulatory approval and societal acceptance. And like clinical trials, the test procedures must assure reasonable protections for workers and other persons exposed to these advances.8 Thus, the introduction of a new technology requires testing by conducting a carefully managed learning process with two main functions: an operational function to discern whether the new product or process can efficiently provide anticipated benefits, and a safety function to identify its risks, which may be latent and unknown at the outset, and to determine if these risks are manageable. Experience in many technological sectors indicates that the safety function is vulnerable to deliberate or inadvertent compromise when it is managed by proponents of the technology who are striving to achieve results which promise personal or organizational gain.9 II. GENE THERAPY TRIALS AND SAFETY ISSUES Carrying out the safety function in clinical trials of new products containing genetically modified materials poses special challenges. Little is known or knowable beforehand about the risks posed by such advances, and many of the human subjects involved have been chosen because of their seriously impaired health, making them especially vulnerable to any risks. Compounding the challenge are contextual circumstances such as the multiplicity of individuals and organizations commonly involved in such a trial, making it a multi-party enterprise in which coordination and communication difficulties may arise and cause responsibilities to become diffuse and uncertain. In addition, there is urgency and pressure for success because of the substantial investment of capital, facilities and human resources over the long period of time usually involved in bringing a biomedical advance to market. 10 The universe of biomedical advances now being tested includes many gene therapies, products containing specially created genetic material to be delivered into target cells of a person with the intention of curing the person's genetically-based illness. …