Faculty Bibliography

Each of K mental health programmes reports the number of patients served in a year. The sum of these numbers, y, is an overcount because some patients are seen in more than one programme. Health care planners need to know the unduplicated number served by the mental health system. Thus, there is an unknown number, M, of distinct individuals who appear on one or more of K lists; some appear on multiple lists and the duplicates are not readily identifiable. Let X be the number of lists on which a randomly selected individual appears. When E(X) is known, y/E(X) is the natural estimator of M. We assume that we know the number of programmes, Xi, used by the ith individual in a random sample of recipients of service. Here, the intuitive estimator, Y/X has desirable statistical properties. We give confidence interval estimators for M. We apply the method to estimate the number of individuals served in 1991 by the mental health programmes in New York State

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

An unexpected finding of the International Pilot Study of Schizophrenia, launched by the World Health Organization (WHO) in 1967, was that patients in countries outside Europe and the United States have a more favourable short- and medium-term course of the disease than those seen in developed countries. Since then, WHO has intensified its schizophrenia research programme and has initiated a set of international studies that have confirmed these initial findings and explored possible reasons for such differences in the course and outcome of schizophrenia. While such work has provided important findings and has generated additional pertinent hypotheses, it did not explain the differences in outcome. The present paper describes a new initiative in which approximately 2500 subjects involved in previous WHO multicentre schizophrenia studies are being followed up for between 15 and 25 years after initial examination. Nineteen research centres in 16 countries are taking part in this work. The research methodology is described

A statistical framework is presented for examining cost and effect data on competing interventions obtained from an RCT or from an observational study. Parameters of the join distribution of costs and effects or a regression function linking costs and effects are used to define cost-effectiveness (c-e) measures. Several new c-e measures are proposed that utilize the linkage between costs and effects on the patient level. These measures reflect perspectives that are different from those of the commonly used measures, such as the ratio of expected cost to expected effect, and they can lead to different relative rankings of the interventions. The cost-effectiveness of interventions are assessed statistically in a two stage procedure that first eliminates clearly inferior interventions. Members of the remaining admissible set are then rank ordered according to a c-e preference measure. Statistical techniques, particularly in the multivariate normal case, are given for several commonly used c-e measures. These techniques provide methods for obtaining confidence intervals, for testing the hypothesis of admissibility and for the equality of interventions, and for ranking interventions. The ideas are illustrated for a hypothetical clinical trial of antipsychotic agents for community-based persons with mental illness

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

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