Clinical research termination

Effects In Humans. Neither postmortem nor functional cerebrospinal fluid (CSF) studies in humans provide firm evidence for similar, long-term damages or alterations to monoaminergic neurons in chronic stimulant abusers. In part, the lack of demonstrable neurochemical changes may well be due to the obvious preclusion of well-controlled prospective experimentation in humans, as well as to variability in critical variables (e.g., individual sensitivity or pattern of abuse) encountered in clinical research. Possible relationship of the various complications of stimulant abuse including hyperpyrexia, seizure, anoxia, and metabolic exhaustion to neuronal chromatolysis, terminal destruction, and monoamine and enzymatic depletion have not been systematically explored in human autopsy eases. It should be also noted that, under nonperturbed conditions, overt behavioral deficits are rare in... 

This is the first time a data base.of this size and degree of comprehensiveness has been compiled on the state of new drug development in any country. We are currently obtaining further information on investigational NCEs, which will include the reasons for termination of clinical research by the firms and full data on licensed compounds. These additional data will clarify some of the trends that have been revealed by the present study, and will allow further analyses to be performed of the reasons behind the observed changes. 

All IRBs are required to maintain records (minutes) of meetings and documents for at least three (3) years after completion of a study. In addition, IRBs are responsible for reporting investigator noncompliance to their institutions, sponsors of clinical research, and the FDA. It is important to note that IRBs have the regulatory authority to suspend or terminate research they previously approved if the research ceases to be conducted in accordance with the IRB s requirements. Research that has been associated with unexpected or serious harm to research subjects may be suspended or terminated. 

In light of the serious side effects of levodopa in Parkinson s disease, Birk-mayer and Hornykiewicz tried to achieve a levodopa-sparing effect by the concurrent administration of levodopa with an MAO inhibitor. As such combinations frequently elicited hypertensive attacks, they were soon compelled to terminate this line of clinical research (Birkmayer and Hornykiewicz 1962). 

Lastly, the ultimate word is always that of clinical successes, and for this reason it is advocated that a network of cancer clinical research centers (CCRCs) be instituted — or the equivalent — to serve initially as a court of last resort for advanced or terminal cancer cases, and later on for any case. These would be primarily staffed by M.D.s and D.O.s, and backed by a system of supportive pharmacologists, biochemists, botanists and ethnobotanists, biologists and zoologists, plus assorted naturopaths and the like — even if considered unconventional, but which are possibly a vital link in the therapeutic chain. 

P-Endorphin. A peptide corresponding to the 31 C-terminal amino acids of P-LPH was first discovered in camel pituitary tissue (10). This substance is P-endorphin, which exerts a potent analgesic effect by binding to cell surface receptors in the central nervous system. The sequence of P-endorphin is well conserved across species for the first 25 N-terminal amino acids. Opiates derived from plant sources, eg, heroin, morphine, opium, etc, exert their actions by interacting with the P-endorphin receptor. On a molar basis, this peptide has approximately five times the potency of morphine. Both P-endorphin and ACTH ate cosecreted from the pituitary gland. Whereas the physiologic importance of P-endorphin release into the systemic circulation is not certain, this molecule clearly has been shown to be an important neurotransmitter within the central nervous system. Endorphin has been invaluable as a research tool, but has not been clinically useful due to the avadabihty of plant-derived opiates. 

Research on an hCG vaccine has been conducted over the past 15 years. WHO has conducted a phase I clinical study in AustraUa, using a vaccine based on a synthetic C-terminal peptide (109—141) of P-hCG conjugated to Diptheria Toxoid (CTP-DT), that showed potentially effective contraceptive levels of antibodies were produced in vaccinated women without any adverse side effects. Phase II clinical studies are under consideration to determine if the immune response, raised to its prototype anti-hCG vaccine, is capable of preventing pregnancy in fertile women volunteers (115). While research on the C-terminal peptide from the P-subunit of hCG has been carried out under the auspices of WHO, research supported by the Population Council and the National Institutes of Health has involved two alternative vaccine candidates (109,116,118). 

The initial studies described above were conducted on Raman microspectrometers on extracted human teeth. In order to translate this research from the laboratory bench to the dental chair side, the next step it is to develop dedicated systems for clinical use. A key element to this development is the use of fibre-optic probes to allow measurements in vivo. We recently reported a study in which optical fibres were used for PRS measurements [48], Although not yet fully realized into a dental probe, this study demonstrated the design and feasibility of acquiring parallel- and cross-polarized Raman spectra via a bifurcated optical fibre whose distal terminal has the two fibres aligned vertically for simultaneously collecting spectra from the two polarization channels on a 2D CCD array. Simultaneous data acquisition will allow for more rapid measurement times in vivo. 

Phase advances of the circadian system and sleep-wake activity have been reported in a number of studies, with daily administration of melatonin (180-183). Termination of melatonin administration resulted in a reversal of the phase advances, with subjects reverting to their preadministration phase. Therefore, continued administration of melatonin may provide a means for those with DSPS to maintain a normal phase, and avoid the associated sleep deprivation due to having to live on a normal schedule. It is important to note, however, that at present the effective dose of melatonin to be administered and the safety of long-term melatonin administration have yet to be established (184). Therefore, melatonin should be thought of as a research compound and not a clinical solution to DSPS. 

Grob extolled the desirability of "using these substances in sanctioned, approved clinical settings." He emphasized that the development of research protocols for the use of psychedelics with individuals suffering from extremely refractory conditions—such as post-traumatic stress syndrome, terminal illness, and severe alcoholism—offers the most likely route toward eventually opening the door to more broadly based research. 

The most enraptured "acid heads are aware that LSD is not—and never can be—a panacea, a solution to all of this planet s problems. This most powerful psychoactive compound hasn t been demonstrated to keep us from aging or to reverse the course of fatal diseases. However, it does without doubt offer important benefits for people confronted with terminal illness. This is an area in which research, particularly at the Veterans Hospital in L.A., the Menninger Clinic in Topeka and Spring Grove Hospital near Baltimore, has impressed skeptics. 

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