End point assessment

E. Therapeutic response The primary end point assessed in four randomized controlled trials was the incidence of complete ulcer closure within 20 weeks. In one study, the incidence of complete ulcer closure for Regranex Gel 0.003% was 48% versus 25% for placebo gel. In another study, the incidence of complete ulcer closure for Regranex Gel 0.01% was 50% versus 36% for Regranex Gel 0.003%. One study failed to detect a difference between Regranex Gel 0.01% and good ulcer care alone. 

End points assessed in a comprehensive 90-day feeding study of pentaBDE (DE-71) in male and female Sprague-Dawley rats included semm T3 and T4 levels (TSH not measured) and thyroid histology (WIL... 

In addition, Fairchild et al. (64) exposed an outdoor stream community consisting of a diverse invertebrate benthic population, Hyallela azteca, and Pimephales promelas. These organisms were exposed to a mean concentration of 0.35 mg/L, a concentration not expected to cause adverse effects if the laboratory-generated NOEC data were protective of the system. End points assessed during the 45-day exposure included a variety of periphytic and benthic invertebrate community measurements. These authors found no effects on the biota contained in this study at 35 mg/L of C12LAS. 

Regulatory Agency End Points Assessed QSAR/Expert System Studied Reference... 

A number of epidemiological studies have been carried out on populations exposed chronically to low doses of MeHg. Table 5-10 summarizes some key methodological aspects of those studies. In this section, those studies are discussed in terms of the end points assessed. End points discussed are status on neurological examination, age at achievement of developmental milestones, infant and preschool development, childhood development, sensory, and neurophysiological functions, and other end points in children. 

DIFFERENCES IN THE NEUROBEHAVIORAL END POINTS ASSESSED AND THE CHILDREN S AGES AT ASSESSMENT... 

Although differences in end points assessed and age of assessment might explain the failure of the SCDS to detect the associations found in the Faroe Islands study, findings from the New Zealand study and the Seychelles pilot study suggest that the discrepancies between the Faroe Islands and the main Seychelles studies are probably not due to differences in the assessments. The New Zealand study found associations between MeHg exposure and scores on the McCarthy Scales of Children s Abilities (the primary outcome measure used in the SCDS) at about the same age of assessment as in the Seychelles study, in a study with full control for potential confounding inflnences. Associations with prenatal Hg exposnre were even seen on the McCarthy scales and the PLS in the 217-member Seychelles pilot study at 5.5 years of age, albeit with only limited control for socioenvironmental inflnences. 

The characteristics of interior paints that require testing and analysis include hiding and appearance, package stabiHty, adhesion, spatter resistance, flow and leveling, color and sheen uniformity, touch-up, stain removal, burnish resistance, and block and print resistance. A popular test that assesses the wet abrasion resistance of an interior paint is to measure its scmb resistance. A mechanical device is used to scmb a paint film of a specified thickness with a standard bmsh and abrasive cleanser suspension. The number of scmb cycles (back and forth movements of the weighted bmsh) at various end points (first cut through, or 50% removal of the film) is then recorded. Scmb resistance usually holds steady or decreases slightly as PVC is increased, but drops quickly once the CPVC is exceeded in a paint formulation. 

Similar results for rats were reported by Crowder et al. (1980). Oral administration of 1 mg/kg/day of methyl parathion (99.9% purity) in com oil on days 7-15 of gestation resulted in increased mortality in pups, relative to controls. Significant difference from controls in a maze transfer test was observed in pups from the treated group. However, use of a single-dose level precluded the assessment of dose-response, and several other behavioral end points were not affected. Furthermore, no information was presented regarding body weights or signs of toxicity in the treated dams. 

Some animal studies indicate that dietary exposure to methyl parathion causes decreased humoral and cellular responses (Shtenberg and Dzhunusova 1968 Street and Sharma 1975). A more recent, well-designed animal study that included a battery of immuno/lymphoreticular end points showed few effects at the nonneurotoxic doses tested (Crittenden et al. 1998). No adequate studies are available in humans to assess the immunotoxic potential of methyl parathion. Therefore, studies measuring specific immunologic parameters in occupationally exposed populations are needed to provide useful information. Further studies are also needed to investigate the mechanism for methyl parathion-induced immunotoxicity since this information would help to identify special populations at risk for such effects. 

The carcinogenic potential of the profiled substance is qualitatively evaluated, when appropriate, using existing toxicokinetic, genotoxic, and carcinogenic data. ATSDR does not currently assess cancer potency or perform cancer risk assessments. Minimal risk levels (MRLs) for noncancer end points (if derived) and the end points from which they were derived are indicated and discussed. 

An effective HE or cost-effectiveness analysis is designed to answer certain questions, such as Is the treatment effective What will it cost and How do the gains compare with the costs By combining answers to all of these questions, the technique helps decision makers weigh the factors, compare alternative treatments, and decide which treatments are most appropriate for specific situations. Typically, one chooses the option with the least cost per unit of measure gained the results are represented by the ratio of cost to effectiveness (C E). With this type of analysis, called a cost-effectiveness analysis (CEA), various disease end points that are affected by therapy (risk markers, disease severity, death) can be assessed by corresponding indexes of therapeutic outcome (mmHg blood pressure reduction, hospitalizations averted, life years saved, respectively). It is beyond the scope of this chapter to elaborate further on principles of cost-effectiveness analyses. A number of references are available for this purpose [11-13]. 

Pharmacoeconomics is a nascent discipline which has not yet provided clinicians and budget managers with the level of information necessary for confident decision-making. This is particularly true in psychiatry where the dearth of acceptable, reliably measurable clinical end points makes pharmacoeconomic evaluation even more complex and open to debate. Nonetheless, the data reviewed in this book, when placed alongside clinical data, do provide a framework for decision-making which is better informed and more realistic than any exclusively clinical assessment could be. Economic evaluations in all major mental illnesses, while some way from conclusive, are certainly providing valuable guidance to decision-makers both at policy level and in the clinic. 

The figures that follow provide examples of some ways in which in vitro clearance data for two series can be compared and assessed to identify key questions, trends, or hypotheses. While the data presented here are for clearance in a human liver microsomal (HLM) incubation, the analysis could be applied in the same way to other data sets - including other experimental ADME or safety end points, or computationally predicted end points. 

Assess subjectively through vital signs and/or facial/body expressions if patient cannot communicate ° Establish predetermined end points... 

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