Clinical trials: are they a good buy?

PURPOSE: Concern that clinical trials may be too costly has been used to justify traditionally restrictive insurer policies regarding clinical trials. Additionally, fear of insurer reimbursement denial can be a significant barrier to clinical trial participation. In this study, we reviewed the empirical data on costs of clinical trials versus standard care and summarized the current status of policy initiatives related to clinical trial insurance reimbursement. METHODS: Electronic and print data sources were searched for studies on the costs of oncology clinical trials. Information on policy initiatives for clinical trial reimbursement was obtained from the American Society of Clinical Oncology, the American Society of Hematology, and the Coalition of National Cancer Cooperative Groups and from searches of World Wide Web sites. RESULTS: Five pilot studies provided information for 377 patients on phase II/III clinical trials matched with controls on standard care. Cost estimates ranged from 10% lower to 23% higher costs/charges for clinical trials in comparison to standard medical care. Medicare, 14 states, and several private insurers now cover the costs of patient care in "qualifying" clinical trials. CONCLUSION: Findings from small pilot studies suggest that phase II and III clinical trials result in at most modest increases in cost over standard treatment costs. Also, an increasing number of policy makers have decided to support clinical trial reimbursement initiatives. It is hoped that economic data from large observational studies will facilitate widespread and permanent decisions that support reimbursement for phase I, II, and III clinical trial participation.

The somatosensory thalamus of the raccoon: properties of single neurons responsive to light mechanical stimulation of the forepaw.

These studies were undertaken to characterize the discharge properties of single neurons of the raccoon thalamic ventrobasal complex (VB) that respond to light mechanical stimulation of the glabrous surfaces of the forepaw. Microelectrodes were used to record the extracellular activity of 146 cells in anesthetized raccoons, and all neurons were histologically verified as falling within or along the boundaries of VB. Sixty-one neurons were tested for activation by electrical stimulaton of primarily somatosensory cortex. Of these, 88% were antidromically activated, 5% were synaptically activated, and the remaining 7% were unresponsive. Out of the total sample of 146 neurons, 136 had peripheral receptive fields (RFs) that were restricted to glabrous skin and revealed properties of modality and place-specificity predictable through knowledge of properties of primary mechanoreceptive afferents. Rapidly adapting (RA) neurons accounted for 77% of this modality-place-specific sample, while 19% were slowly adapting (SA), and 4% revealed properties indicative of input from Pacinian afferents (Pc). Absolute displacement thresholds were comparable for RA and SA neurons (range = 6-415 micron). Palmar RF areas (range = 3.3-328 mm2) were significantly larger than digital RF areas (range = 0.5-98.2 mm2). As defined by exponents (b) of power functions relating instantaneous discharge frequency to displacement ramp velocity, SA neurons formed a single, homogeneous group (range of values of b = 0.633-0.720). However, RA neurons fell into three distinct groups: those showing relatively steep functions (b = 0.559-0.938), those showing relatively flat functions (b = 0.146-0.334), and those showing discontinuous, or step, functions. A small number of neurons (7% of total sample) revealed "complex" properties, not predictable from knowledge of properties of primary afferents. These included five neurons whose RFs encompassed both glabrous and hairy skin, and several linear orientation, or "tactile edge," detectors. The present results, in conjunction with those of earlier studies of the raccoon dorsal column-medial lemniscal system, lead to the conclusion that different types of information transformation are emphasized at different levels of the system. Intramodality convergences (increases in RF area) occur primarily within the cuneothalamic relay, while changes in the coding of quantitative information are primarily a function of VB neurons. The appearance of linear orientation detectors--a type of tactile "feature detector"--indicates that the synthesis of information regarding complex spatial properties of stimuli has its beginnings within the somatosensory thalamus.

Time-dependent changes in the functional organization of somatosensory cerebral cortex following digit amputation in adult raccoons.

Surgical removal of the third forepaw digit in raccoons causes both long-term and short-term changes in functional organization within the digit 3 primary somatosensory (SmI) cortex. Previous studies have shown that 36-52 weeks following amputation in infant raccoons, neurons within the digit 3 cortical territory had become responsive to cutaneous stimulation of "new" forepaw regions adjoining the digit stump (Carson et al., 1981; Kelahan et al., 1980, 1981); the "novel" receptive fields (RFs) were often larger than normal and revealed no orderly somatotopic organization. In the present study, the cortical effects of digit 3 removal were examined in adult raccoons. Within 36 weeks after amputation, the digit 3 zone was also found to be reactivated by "novel" inputs from the forepaw, with no strictly topographic representation of the "new" skin fields. The basic features of cortical reactivation were very similar in animals amputated as adults and as infants, except that the former typically had larger neuronal RFs than the latter. Short-term cortical changes were studied in adult raccoons within 1 day and between 1 and 4 weeks after amputation: Significant time-dependent differences were found in the reactivated digit 3 territory. Within 1 hr following amputation, some cells in the digit 3 zone began to respond to low-intensity cutaneous stimulation of "new" forepaw regions, limited almost exclusively to digits 2 and 4. Neuronal RFs tended to be larger than normal and showed no strictly topographic organization. One to 4 weeks following amputation, the condition of the digit 3 zone differed dramatically from that found immediately and long after amputation--the majority of responsive neurons could be excited only by high-intensity stimulation of small RFs on the digit 3 stump; relatively few cells were sensitive to low-intensity stimulation of adjacent, intact skin regions. Again, no true somatotopic organization was evident. The combined results of these experiments indicate that within 36 weeks following removal of a digit in raccoons, the deprived SmI cortical sector undergoes a dynamic sequence of changes in functional organization: Neurons that are normally excited by stimulation of digit 3 first become responsive primarily to stimulation of digits 2 and 4 (within 1 day after amputation), then to the digit 3 stump (from at least 1-4 weeks after amputation), and finally again to digits 2 and 4 (within at least 36 weeks after amputation).(ABSTRACT TRUNCATED AT 400 WORDS)

Functional reorganization of adult raccoon somatosensory cerebral cortex following neonatal digit amputation.

Amputation of a forepaw digit in raccoons 2-8 weeks of age produced dramatic changes in the functional organization of somatosensory cortex examined electrophysiologically 9-12 months later. The cortical region normally representing the digit that was amputated received widely overlapping input from the entire forepaw, with local disruption of somatotopic organization. Compared with normal animals, the receptive fields of cortical neurons in amputated animals were larger, often included both glabrous and hairy skin, sometimes involved discontinuous skin regions, and were much more variable in peripheral location as a function of recording distance across the cortex and of depth within the cortex.