Efficacy variable

Allosteric antagonism with changes in efficacy variable slope... 

Allosteric Antagonism with Changes in Efficacy Variable Slope... 

Cyproheptadine Antagonizes serotonin 20-32 mg/day Sedation, increased Efficacy variable. 

Efficacy variables are chosen according to the objectives of the trial. They may be the therapeutic effect itself (e.g. irradication of infection, healing of peptic ulcer) or a factor related to the therapeutic effect or some surrogate effect. 

AU randomised patients with at least one dose of study drug and at least one observation of the efficacy variable after baseUne. 

Bromazepam. Another benzodiazepine, bromazepam, which is not currently available in the United States, was the subject of an open trial by Versiani et al. [1989]. In this study, 10 subjects with social phobia received the agent over an 8-week period, with a mean dose of 26.4 mg/day. All efficacy variables demonstrated statistically significant improvement at week 8 compared with baseline scores. However, all subjects reported sedation as a side effect, and 4 of 10 subjects reported memory disturbance. 

The initial study of clonazepam in social phobia conducted by Versiani et al. [1989] showed an overall benefit of the drug. This 8-week, open trial of 40 subjects displayed statistically significant lowering of scores on the efficacy variables, which included the Clinical Global Improvement and Severity Scales [Guy 1976], Liebowitz Social Anxiety Scale [liebowitz 1987], Hamilton Anxiety Scale [M. Hamilton 1959], and the Sheehan Disability Scale [D. V. Sheehan 1986]. The mean dose of clonazepam was 3.9 mg/day [SD 0.5 mg]. Subjects in this study reported high rates of side effects, including sleepiness [67.5%], loss of libido [67.5%], and memory problems [35%]. 

Stevia Stevia rebaudiana) Uses Natural sweetener, hypoglycemic and hypotensive properties Actions Multiple chemical components sweetness d/t glycoside, stevioside hypotensive effect may be d/t diuretic action or vasodilation action Available forms Liq extract, powder, caps Notes/SE HA, dizziness, bloating Interactions T Hypotensive effects W/ antihypertensives esp CCB, diuretics EMS Monitor BP does not encourage dental caries may -1-glucose St. John s Wort (Hypericum perforatum) Uses Mild-mod depression, anxiety, anti-inflammatory, immune stimulant/anti-HIV/antiviral, gastritis, insomnia, vitiligo Action MAOI in vitro, not in vivo bacteriostatic bactericidal, T capillary blood flow, uterotonic activity in animals Efficacy Variable benefit w/ mild-mod depression in several trials, but not always seen in clinical practice Available forms Teas, tabs, caps, tine, oil ext for topical use Dose 2-4 g of herb or 0.2-1 mg of total hypericin (standardized extract) daily Notes/SE Photosensitivity (use sunscreen) rash, dizziness, dry mouth, GI distress Interactions Enhance MAOI activity, EtOH, narcotics, sympathomimetics EMS T Risk of photosensitivity Rxns t effects of opioids and sympathomimetics... 

Variables that will serve to monitor safety and those that will document efficacy should be justified as those most likely to provide complete information. The primary efficacy variables should be identified, and those that are secondary should be named as such. 

The report should also contain data tabulations for all primary and secondary efficacy variables. 

Intramuscular ziprasidone has recently been compared with intramuscular haloperidol in the treatment of acute psychosis for a very short period (66). Patients were randomly allocated to intramuscular ziprasidone for up to 3 days of flexible dosing (n = 90 last oral daily dose 91 mg) or haloperidol (n = 42 last oral daily dose 14 mg) followed by oral treatment to day 7. Mean reductions from baseline in all efficacy variables were significantly greater with ziprasidone than with haloperidol at the end of the study. The percentage of patients who had any adverse event was lower with ziprasidone (46%) than with haloperidol (60%) most of the adverse effects were mild or moderate. Four patients discontinued ziprasidone owing to adverse events compared with one in the haloperidol group. 

Large simple Very common disease Easily measured end-points Well-understood drug Tolerability issues not closely related to efficacy variable... 

Major safety and efficacy variables (to be decided and documented in advance). It is not necessary for all measured variables to be recorded in the medical file. Present and future clinical care of the study subject is the most important factor in determining whether or not measured variables should be recorded in the medical file. The investigator should record what he/she would normally record to care for the study subject, but also take into account any recording needed because of the special circumstances of a clinical study. The entire medical file should be reviewed to ensure that no additional information exists in the medical file that should have been recorded in the CRF... 

For example In a placebo-controlled clinical trial for testing a new analgesic for treatment of migraine headaches, the key efficacy variable is the number of subjects whose headache is eliminated within 1 h of treatment. A statistical model appropriate for this situation is as follows ... 

Suppose one wishes to conduct a trial to test the efficacy of a new antihypertensive drug. The clinical research physician plans to enroll a certain number of subjects with mild to moderate hypertension and randomize them to receive either the experimental drug or placebo. The primary efficacy variable is the decrease in the diastolic blood pressure as compared to a pretreatment baseline. 

The a priori identification of specific risk hypotheses leads to the ability to take some of the methodology normally applied to hypothesis testing of efficacy results and apply it to safety assessment. The most important difference between these two analysis domains is that in the case of efficacy, outcomes of interest are identified a priori with great specificity, and clear statistical hypotheses are laid out in advance with complete analysis and decision rules documented in the clinical protocol. In practice, only a few efficacy variables are identified as primary, and only a few others as second-ary. Sensitivity, statistical power, and sample size are all carefully analyzed in advance to assure the trial will have a high probability of detecting differences of interest in these few critical variables. 

The primary efficacy variable was mean change from baseline in best-corrected log MAR visual acuity. Secondary efficacy variables included the percentage of patients with stable vision (< 3 log MAR lines of visual acuity decrease from baseline) and assessments of size of both the CNV and classic CNV lesion components. Clinical data was assessed at days 1-2, week 2, week 6, month 3, and month 6 following therapy. A 6-month retreatment interval was established based on the laboratory data confirming therapeutic levels of the drug in the retina and choroid for up to six months. The data reported in the 6-month interim study, however, reflects a single administration. 

A common type of pharmacodynamic variable is where the response is not continuous, but qualitative. At its most simple extreme, the response either occurs or does not occur and the variable itself is said to be binary or dichotomous. In this case, the response can be coded using an indicator variable 0 for the event does not occur or 1 for the event does occur. Many types of pharmacodynamic measures of this kind can be found, most notably with safety and efficacy variables. Theoretical and practical considerations indicate that when the pharmacodynamic measure is binary, the shape of the response function should be curvilinear. 

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