Session XII Male contraception

Session XII Male contraception     

An optimal three-stage design for phase II clinical trials

A phase II clinical trial in cancer therapeutics is usually a single-arm study to determine whether an experimental treatment (E) holds sufficient promise to warrant further testing. When the criterion of treatment efficacy is a binary endpoint (response/no response) with probability of response p, we propose a three-stage optimal design for testing H₀: p ≤ p₀ versus H₁: p ≥ p₁, where p₁ and p₀ are response rates such that E does or does not merit further testing at given levels of statistical significance (α) and power (1 ? β). The proposed design is essentially a combination of earlier proposals by Gehan and Simon. The design stops with rejection of H₁ at stage 1 when there is an initial moderately long run of consecutive treatment failures; otherwise there is continuation to stage 2 and (possibly) stage 3 which have decision rules analogous to those in stages 1 and 2 of Simon's design. Thus, rejection of H₁ is possible at any stage, but acceptance only at the final stage. The design is optimal in the sense that expected sample size is minimized when p = p₀, subject to the practical constraint that the minimum stage 1 sample size is at least 5. The proposed design has greatest utility when the true response rate of E is small, it is desirable to stop early if there is a moderately long run of early treatment failures, and it is practical to implement a three-stage design. Compared to Simon's optimal two-stage design, the optimal three-stage design has the following features: stage 1 is the same size or smaller and has the possibility of stopping earlier when 0 successes are observed; the expected sample size under the null hypothesis is smaller; stages 1 and 2 generally have more patients than stage 1 of the two-stage design, but a higher probability of early termination under H₀; and the total sample size and criteria for rejection of H₁ at stage 3 are similar to the corresponding values at the end of stage 2 in the two-stage optimal design.     

Ethical dilemmas in today's nuclear medicine and radiology practice.

Throughout history, societies have developed their own codes of ethics, including those pertaining to the practice of medicine. In the United States, physicians have adopted a set of ethics based on religious values and historical teachings. We, as physicians, have been presented several codes of ethics, including the American Medical Association Code of Ethics and the American College of Radiology Code of Ethics. Over time, we have learned to appropriately apply these codes to our daily practice. With the advent of new technologies in imaging, we may lose sight as to the transfer of these principles to reflect current conditions. Recent history has shown a trend of new technology leading to potential misuse of this technology and further leading to stricter governmental regulations. It is the purpose of this review to give guidelines for dealing with new technologies, such as PET imaging, and we describe a radiologist's ethical responsibility in a doctor-patient relationship. A historical review of medical ethics will lead to discussions about various issues affecting radiologists and nuclear physicians. To be sure, not all ethical situations are black and white, and therefore there are many gray areas. The opinions expressed in this article are those of the authors and are based on extension of already established rules of ethical conduct.     

Effect of cisplatin chemotherapy on extracortical tissue formation in canine diaphyseal segmental replacement

The reconstruction of large bone and joint defects after the resection of malignant tumors remains a major challenge. Chemotherapy has significantly lowered the risk of metastasic disease, but complications associated with reconstructive techniques continue to result in late morbidity. In the present study, biomechanical torsion testing, gait analysis, and histomorphometric and scanning electron microscopic evaluations of 24 dogs were used to examine the effects of preoperative and postoperative administration of cisplatin on the biologic fixation of a porous-coated segmental replacement prosthesis. The chemotherapy consisted of four cycles of cisplatin administered at a dosage of 75 mg/m:² preoperatively or postoperatively. The healing was enhanced by use of an autogenous corticocancellous bone graft. The graft was placed evenly around the prosthesis and the adjacent femoral cortex. Mechanical analyses of torsional stiffness, yield strength, and maximum strength revealed no statistically significant differences between the groups at 12 weeks. Such lack of difference was mainly due to the penetration of highly organized fibrous tissue into the porous surface; this provided strong fixation of the implant to bone even in the absence of bone ingrowth. Although bone ingrowth into the prostheses was not affected, electron microscopic, histomorphometric, and radiologic analyses showed a clear difference in the formation of new bone around the prosthesis. Preoperative chemotherapy did not alter the formation of new bone, but specimens from animals treated postoperatively with cisplatin showed significantly less bone graft resorption and less new bone formation. Hence, the effect of cisplatin administration caused only a temporary delay, not a permanent effect, on extracortical capsule formation. The formation of extracortical bone and soft tissue might prevent debris-incised osteolysis and, therefore, prevent late complications by forming a tight capsule around the bone-prosthetic interface.     

Corneal tissue mass in normal and keratoconic eyes. In vivo estimation based on area of horizontal optical sections

Based on measurements of the corneal diameter, radius of curvature variation, and thickness profile a method for calculation of the horizontal meridian's sectional tissue mass area (M) is described. Pooled values of 52 normal eyes demonstrate M to be 8.57 mm2 +/- SD. Comparing one eye of 27 keratoconic patients with one eye of 28 normals established no significant difference in M. This result is in accordance with a hypothesis in which the keratoconic corneal thinning is a result of an increased sliding of collagen fibers rather than a result of increased collagen degradation.