Carole Siegel

The correlation between blood levels of ibuprofen and clinical analgesic response

A clinical trial comparing ibuprofen, 400, 600, and 800 mg, with aluminum ibuprofen, 400 mg, and placebo was conducted in patients with moderate or severe pain subsequent to third molar extraction. Pain intensity ratings and ibuprofen serum levels were obtained at baseline, 30 minutes, 1 hour, and hourly thereafter for 3 hours. Pain intensity ratings were also obtained at hours 4, 5, and 6. Serum levels at 1, 2, and 3 hours correlated significantly with the log dose of ibuprofen (r = 0.35, 0.49, and 0.48, respectively) and with global analgesic response as measured by the percentage of the sum of the pain intensity scores (r = 0.28, 0.34, and 0.26, respectively). However, possibly because of differences in drug formulation, the percentage of the sum of the pain intensity scores did not correlate significantly with log dose. The highest correlations were found between contemporaneous serum levels and pain intensity difference values, particularly at hour 1 (r = 0.54). Our results support the proposition that increased ibuprofen serum levels lead to increased analgesia.

Tenant Outcomes in Supported Housing and Community Residences in New York City

OBJECTIVE This study examined whether outcomes in housing, clinical status, and well-being of persons with severe mental illness and a history of homelessness differ between those in supported housing and those in community residences, two housing arrangements that substantially differ in the level of independence that is offered to its tenants. METHODS A quasi-experimental 18-month follow-up study was conducted with 157 persons newly entering supported housing and community residences. The housing models accepted persons with similar illness characteristics and homelessness histories, so that the inability to randomly assign tenants to housing types could be compensated for by propensity scoring methods. Tenure in housing was examined by using survival models. Analyses of other outcomes used hierarchical linear and regression models in both intent-to-treat (N=139) and true-stayer (N=80) analyses. RESULTS Tenure in housing did not differ by housing type. Substantial proportions of tenants in both models remained housed during the follow-up period. Tenants in supported housing reported greater housing satisfaction in terms of autonomy and economic viability. Over time some tenants in supported housing reported greater feelings of isolation. Independent of housing type, symptoms of depression or anxiety at housing entry increased the risk of poorer outcomes. CONCLUSIONS The models of supported housing were viable portals of entry into community housing for homeless persons, even for consumers with characteristics indicating that they would have been more likely to be placed in community residences. The results suggest that greater clinical attention should be paid to persons who exhibit depression or anxiety when entering housing.

Statistical inference for cost-effectiveness ratios.

Methods for statistical inference for cost-effectiveness (C/E) ratios for individual treatment and for incremental cost-effectiveness (delta C/ delta E) ratios when two treatments are compared are presented. In a lemma, we relate the relative magnitude of two C/E ratios to the delta C/ delta E ratio. We describe a statistical procedure to test for dominance, or admissibility, that can be used to eliminate an inferior treatment. The one-sided Bonferronis confidence interval procedure is generalized to the two-sided case. The method requires only that two confidence intervals be available, one for cost and one for effectiveness. We describe Fieller-based confidence intervals and show them to be shorter than Bonferroni intervals. When distribution assumptions hold and variance and covariance estimates are available, Fieller intervals are preferable. However, Bonferroni intervals can be applied in more diverse situations and are easier to calculate. A simple Bonferroni based technique, and a likelihood ratio statistic given by Siegel, Laska and Meisner, for testing the null hypothesis that the C/E ratios of two treatments are equal is presented. The approaches are applied to the data from a phase II clinical trial of a new treatment for sepsis considered previously by others.

ONSET AND DURATION : MEASUREMENT AND ANALYSIS

Clinical Pharmacology and Therapeutics (1991) 49, 1–5; doi:10.1038/clpt.1991.1

MATCHED-PAIRS STUDY OF RESERPINE USE AND BREAST CANCER

This paper reports on an analysis of psychiatric population. 55 female patients with breast cancer were matched with non-cancer patients on age, year of admission, psychiatric diagnosis, race, and religion. Reserpine use was examined for yearly use by each year preceding the diagnosis of breast cancer, by cumulative yearly use, and by other defined time periods. Regardless of the definition of reserpine user, there were no significant increased relative risks of breast cancer for those women on reserpine. There was a fairly low proportion of patients from each group who were on the drug in any given year, and a fairly wide range of total dosage received. Over half of the women used reserpine at some time during their hospital stay.

Performance measures of cultural competency in mental health organizations.

The authors utilized numerous documents created by advisory groups, expert panels and multicultural focus groups to develop performance measures for assessing the cultural competency of mental health systems. Competency was measured within three levels of organizational structure: administrative, provider network, and individual care-giver. Indicators, measures and data sources for needs assessment, information exchange, services, human resources, plans and policies, and outcomes were identified. Procedures for selection and implementation of the most critical measures are suggested. The products of this project are broadly applicable to the concerns of all cultural groups.

A bioassay computer program for analgesic clinical trials

A Fortran program to calculate estimates of relative potency of a test to a standard analgesic is described. The program considers, at the option of the users, four distinct populations: completers, all of those patients who have completed a full crossover round of medication; two‐rounders, patients who have completed two or more rounds of medication; incompleters, patients who have not completed one or more rounds of medication; and first dose only patients, the initial administration received by all patients in the study whether or not they have dropped out. Up to six observations plus the initial reading for pain intensity scores and pain relief scores may be processed separately. The program also creates several summary variables including: SPID, an estimate of the area under the reciprocal of the pain intensity curve; TOTAL, an estimate of the area under the pain relief curve; and estimates of onset and duration as measured by relief scores and by pain intenSity scores. The program automatically performs calculations‐ for the analysis of variance and produces F values when appropriate for testing linearity of the log dose relationship, parallelism of the two curves for test and standard, and so forth. The paper discusses the rationale behind the approach adopted in the program.

Simple Designs and Model-free Tests for Synergy

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.

Performance measures and their benchmarks for assessing organizational cultural competency in behavioral health care service delivery.

A project is described in which performance measures of cultural competency in behavioral health care were selected and benchmarked. Input from an Expert Panel representing the four major ethnic and racial groups in the U.S. and persons with extensive experience in implementing cultural competency in health care, along with survey data from 21 sites were used in the process. Measures and benchmarks are made specific to organizations that administrate care networks, and to service entities that deliver care. Measures were selected to parallel an implementation process, and benchmarks were set at “gold standard” levels.

POWER AND SAMPLE SIZE IN COST-EFFECTIVENESS ANALYSIS

For resource allocation under a constrained budget, optimal decision rules for mutually exclusive programs require that the treatment with the highest incremental cost-effec tiveness ratio (ICER) below a willingness-to-pay (WTP) criterion be funded. This is equivalent to determining the treatment with the smallest net health cost. The designer of a cost-effectiveness study needs to select a sample size so that the power to reject the null hypothesis, the equality of the net health costs of two treatments, is high. A recently published formula derived under normal distribution theory overstates sample- size requirements. Using net health costs, the authors present simple methods for power analysis based on conventional normal and on nonparametric statistical theory. Key words: cost-effectiveness analysis; power; sample size; cost-effectiveness ratios; net health costs; net health benefits; statistical analysis. (Med Decis Making 1999;19: 339-343)