Faculty Bibliography

Alzheimer's disease (AD) is associated with an increased mortality in comparison with aged control populations. The relationship between the clinical and the temporal course of AD has not been well studied over significant intervals. Community-residing patients with probable AD (N = 103, 42 men, mean age = 70.2 +/- 8.0 years) were studied at baseline on demographic and clinical variables, including measures of global deterioration (Global Deterioration Scale; GDS), mental status and cognition (e.g., Mini-Mental State Examination; MMSE), and functional impairment (Functional Assessment Staging; FAST). Baseline characteristics included a GDS range of Stage 4, 5, or 6 (38.8%, 39.8%, and 21.4%, respectively) and a mean MMSE score of 15.4 +/- 5.6. The mean follow-up interval was 4.6 +/- 1.4 years. Follow-ups were done blind to baseline measures and when necessary were conducted in residential and nursing home settings. Of locatable subjects (n = 95, 92%), 30 (31.6%) were decreased. Survivors (n = 65) had a mean GDS stage of 6.2 +/- 0.9 and a mean MMSE score of 5.1 +/- 6.9; 51% had MMSE scores of 0. Increased age and male gender, but not baseline clinical dementia variables, increased the risk of death (ps < .01). Change in clinical variables correlated significantly with time elapsed (r = .32, p < .05, for MMSE change, to r = .48, p < .001, for GDS change). Significant variance in temporal change (i.e., time elapsed) was accounted for by change in two of the five clinical measures studied (i.e., GDS and FAST; multiple r = .53). The results support previous estimates of mean duration of the GDS and FAST stages. For subjects with probable AD followed over approximately 5 years, clinical variables changed significantly over time in survivors. However, the majority of temporal variance in the course of AD remains unexplained

For antipsychotic phase 3 clinical trials, we compare the relative merits of a placebo washout period with an alternate design strategy using a low-dose antipsychotic treatment. Evaluations are made with respect to the achievement of specific clinical trial design goals including the effect on power for detecting between-treatment and within-treatment pre-post differences. The relative merits of these two designs are discussed separately for those patients who enter the initial leadin period after withdrawal from previous antipsychotic medication and for those not on medication immediately before that period

In addition to describing treatment efficacy in terms of changes in rating scale scores, the distributions of time to occurrence of major clinical events such as onset and response are clinically important information. Issues in the design, conduct and analysis of clinical trials in which the time to onset of effect or time to response is to be characterized are discussed. A criterion must be defined to signal that the clinical event has occurred. Onset properties are given in terms of (1) the probability of obtaining onset and (2) for patients who obtain onset, the distribution of time to onset. A statistical model and methods to estimate parameters and compare onset times of treatments are described. A simple formula that can be used to aid in clinical decision making as to when to alter treatment if onset has not yet occurred is presented

The effects of d-amphetamine (0.5 mg/kg orally) on regional cerebral glucose utilization were measured with positron emission tomography (PET) in 17 schizophrenics (along with a placebo-control group of an additional six schizophrenic patients). The acute d-amphetamine challenge tended to decrease glucose utilization throughout much of the brain, with a regional effect that was statistically significant in the left temporal cortex. There was no apparent relationship between the effects of amphetamine-induced changes in regional cerebral metabolism and psychotic symptom exacerbation. An exploratory analysis suggested that features characteristic of Crow's type II syndrome were significant predictors of cerebral hyporesponsivity to stimulant challenge, however

Current statistical designs for studying whether two or more agents in combination act synergistically nearly always require the study of several doses of many dose ratios. The analysis is usually based on an assumed parametric model of the dose-response surface. In this paper, for both quantal and quantitative response variables, sufficient conditions are given for establishing synergy at a dose of the combination without the need to specify the model. This enables the use of simple designs with few doses even when there is sparse knowledge of the dose-response curves of the individual agents. The Min test, used for testing whether an identified treatment is best, may be used for testing synergy. Power issues are discussed

To estimate the size of a population a plant-capture method, an alternative to the classic capture-mark-recapture model, is presented. Known or marked individuals otherwise indistinguishable from the remainder of the population are planted followed by an effort to capture members from the augmented population. Maximum likelihood estimators and a confidence region together with the expected length of the confidence interval for the size of the population as a function of the number of plants are given. A methodology for comparing the cost efficiency of plant-capture to capture-recapture is developed. An application to counting the homeless is given

Nonparametric generalized maximum likelihood product limit point estimators and confidence intervals are given for a cure model with random censorship. One-, two-, and K-sample likelihood ratio tests for inference on the cure rates are developed. In the two-sample case its power is compared to the power of several alternatives, including the log-rank and Gray and Tsiatis (1989, Biometrics 45, 899-904) tests. Implications for the use of the likelihood ratio test in a clinical trial designed to compare cure rates are discussed

This study explored the relationships between plasma levels and the clinical effects of haloperidol in 176 acutely exacerbated schizophrenic or schizoaffective patients. After a single-blind placebo period of 1 week (period 1), they entered the double-blind period 2 randomly assigned to one of three plasma levels of haloperidol: low (2 to 13 ng/mL), medium (13.1 to 24 ng/mL), or high (24.1 to 35 ng/mL). Patients whose conditions did not improve in period 2 continued on one of the three haloperidol levels (period 3). Periods 2 and 3 lasted 6 weeks each. Only minor differences in clinical responses were noted among the three levels of haloperidol. These results imply that low or moderate doses of neuroleptics are appropriate for many acutely psychotic patients

We suggest that a desirable form for prospective payment for inpatient care is hospital average cost plus a linear combination of individual patient and national average cost. When the coefficients are chosen to minimize mean squared error loss between payment and costs, the payment has efficiency and access incentives. The coefficient multiplying patient costs is a hospital specific measure of financial risk of the patient. Access is promoted since providers receive higher reimbursements for risky, high cost patients. Historical cost data can be used to obtain estimates of payment parameters. The method is applied to Medicare data on psychiatric inpatients