Thaddeus E. Prout

Patient recruitment techniques in clinical trials

Recruitment is never easy, but insurmountable difficulties may arise if this problem is not addressed during the planning phase. Preparation for recruitment must then be started long before the study actually begins. These preparations include building local interest in the participating hospital, visiting local hospitals and medical groups, and informing the general public when feasible. As active recruitment begins, access to the study must be kept open and logistical problems must be solved on a daily basis. Frequent reassessment may demonstrate a failure to maintain goals. Innovative methods for reviving the campaign must then be put in place. Above all, share all successful recruitment methods with others in the study.

The antigenicity of insulin: A review

Observations of the antigenic properties of insulin have been reviewed. The antibody responsible for skin sensitivity to insulin is heat-labile and can be obtained from the beta-globulin fraction of serum from affected individuals. A second antibody has been described which is heat-stable and can be demonstrated in the gamma or intra-beta-gamma globulin in most individuals previously treated with insulin. Numerous methods have been described for the detection of insulin antibodies in vitro. It is not possible to decide on the basis of present information whether the in vitro tests indicate the presence of a single or of multiple antibodies to insulin. Some of the problems concerning the relation between insulin antibodies and the use of insulin in the treatment of diabetic patients have been discussed.

The ethics of informed consent.

Informed consent is vital to the conduct of clinical trials. The evolution of this process is reviewed. In the United States, specific steps must now be taken to assure institutional review bodies that all precautions have been taken to inform patients before they are enrolled in studies. These include (1) the procedure to be followed in the study, (2) the benefits for the individual, (3) the discomforts and risks that are reasonably expected, (4) the alternative methods of therapy, (5) the willingness of the investigator to answer inquiries, and (6) the right to refuse or to withdraw from the study without prejudice. The conditions are discussed in detail.

CONGENITAL DEAFNESS AND GOITER. STUDIES OF A PATIENT WITH A COCHLEAR DEFECT AND INADEQUATE FORMATION OF IODOTHYRONINES.

Abstract A twenty-eight year old euthyroid Negro woman was studied for congenital deafness and goiter. The ability of her thyroid gland to accumulate radioiodine was normal. Dehalogenase activity was also normal, since monoiodotyrosine given orally was deiodinated at a normal rate. No abnormal iodoproteins were found in the thyroid gland, serum or urine. In contrast to previously described deaf patients with goiter, this subject was able to iodinate tyrosine. No thyroxine was found in a concentrated hydrolysate of thyroid tissue, although normal concentrations of thyroxine were present in serum. It is postulated that this patient has a partial defect in the condensation of iodotyrosines to form iodothyronines and that whatever thyroxine and triiodothyronine her gland did synthesize were rapidly released. Alternative hypotheses which cannot be excluded by the studies are considered. Seven other nondeaf goitrous subjects had reduced but measurable quantities of iodothyronines in their thyroid glands. Although the goitrous deaf subject had an intact vestibular apparatus, audiometric studies revealed total loss of hearing. Direct stimulation showed the absence of cochlear and eighth nerve action potentials. This suggests that the hearing loss is secondary to disease of the organ of Corti. Congenital deafness and goiter is a heritable disorder, but the precise relationship of one defect to the other is unknown.

Determination of the rate of insulin destruction in vivo.

Insulin given by intravenous injection disappears rapidly from the plasma. The half time of insulin labeled with iodine-131 (I131) in the intravascular space has been shown to be approximately twenty-five minutes. The rapid decline in plasma concentration is the result of several events that occur simultaneously: first, insulin undergoes proteolytic destruction in the liver and kidney;2 second, insulin may be bound or sequestered by tissue cells;3 and, third, insulin may be dispersed in the compartments of body water. The experiments reported in this paper were designed to determine the extent to which each of these processes affects insulin disappearance.