Search PubMed⌕ Search

Biomedical subjects

J E Overall

Publications and source records attributed to J E Overall.

At least 55 records · Page 3Linked to original sources
PubMed1991

Baseline corrections in experimental and quasi-experimental clinical trials.

Three methods of correcting for baseline differences are evaluated for use with randomized experimental designs and nonrandomized quasi-experimental designs. Cases where baseline means differ significantly in spite of random assignment and cases where observed baseline means do not differ significantly in quasi-experimental designs are given special attention. For comparison of treatment-induced change in randomly constituted treatment groups, analysis of covariance (ANCOVA) provides appropriate type I error protection and superior power regardless of the apparent significance of chance baseline differences. Correcting for baseline differences by expressing outcome scores as percentage of the baseline value for each individual produces results that closely approximate ANCOVA under specified conditions. Tests on simple pre-post difference scores are nonconservative when baseline means differ significantly in spite of randomization. In quasi-experimental research where treatment groups represent samples from different predefined populations, ANCOVA and percentage change provide inadequate baseline corrections even when the observed baseline means do not differ significantly. Although no method of baseline correction is entirely satisfactory in the absence of random assignment, tests on simple pre-post difference scores are generally superior for quasi-experimental designs in which treatment groups represent samples from different populations.

Analysis of Variance↗
PubMed1991

Factors related to haloperidol response and dyskinesias in autistic children.

A secondary analysis of data pooled from three studies (Anderson et al. 1984, 1989; Campbell et al. 1978) was performed to identify variables predictive of haloperidol response in 125 autistic children, with ages ranging from 2.3 to 8.2 years. Mean behavioral improvement was greater under haloperidol treatment conditions than under placebo. Higher intelligence quotient (IQ) was predictive of reduction in behavioral symptoms under general conditions of haloperidol or placebo treatment, while older children were found to respond favorably to haloperidol itself. Under both haloperidol and placebo conditions, there was also a tendency for greater reduction in symptoms, in terms of raw score and percent change, for those with greater initial severity of illness. Results for initial severity of illness as a predictor of improvement generalized across a wide variety of behavior not specific to autism (e.g., hyperactivity and temper outbursts). However, mean behavioral improvement and its prediction with demographics for individuals tended to be more specific to symptoms related to autism per se. Reduction in symptoms during short-term haloperidol treatment was not found to be related to whether or not children developed dyskinesias in subsequent long-term haloperidol administration.

Autistic Disorder↗
PubMed1990

Predicting the posttreatment depressive state of an alcoholic patient.

Seventy-eight patients admitted to an alcohol treatment program were studied to identify variables capable of forecasting a patient's posttreatment depressive state. Factor analysis reduced a large number of items to 12 factors. Pearson correlations showed that Factor VII--Physical and Neurological Complaints and the pretreatment depressive state were both significantly (p = .002) correlated to the posttreatment depressive state. Multiple regression yielded a significant equation (p = .001) confirming that an alcoholic patient who has a high level of pretreatment depression and physical/neurological complaints, and who exhibits little or no irritability or agitation will tend to sustain a high level of posttreatment depression.

Adult↗
PubMed1990

Stereotypies and tardive dyskinesia: abnormal movements in autistic children.

Baseline stereotypic movements in 224 autistic children were studied as well as their relationship to certain demographic variables and measures of overall symptomatology and severity of illness. Prediction of haloperidol-related dyskinesias with measures of stereotypies and demographic variables was also attempted. Stereotypies were present in at least mild form in most children, with most showing moderate severity. Most stereotypies were in the orofacial area. I.Q. was found to be negatively related to stereotypies. Furthermore, across methods of assessment, severity and frequency of stereotypies were found to be positively related to overall symptomatology and severity of illness. No significant predictors of development of dyskinesias were found.

Adolescent↗
PubMed1990

Tests of one-sided versus two-sided hypotheses in placebo-controlled clinical trials.

The p value associated with a test of significance is supposed to represent the probability of observed results given that the null hypothesis is actually true. In evaluating the efficacy of a new drug against placebo, regulatory considerations focus on superiority of the new drug over placebo. The disapproval consequence of placebo superiority is no different from the disapproval consequence of equivalence between drug and placebo. It is furthermore inconceivable that a drug company will submit a New Drug Application claiming superior efficacy for placebo. Thus, the only probability of concern is the probability that apparent superiority of drug over placebo is a chance finding, and that is the probability associated with a one-tailed test. Where multiple studies must be evaluated with regard to the regulatory decision, meta-analytic considerations further support the relevance of one-sided p values.

Analysis of Variance↗
PubMed1989

The superiority of a drug combination over each of its components.

The requirement for approval of a combination drug treatment AB is its demonstrated superiority over each of its components A and B at their most appropriate dose levels. This has led to frequent use of a three-group experimental design that permits separate testing of H0:AB less than or equal to A and H0:AB greater than or equal to B. A type I error can occur if no true treatment effect is present in either or both of the contrasts. The sampling distribution for the larger of the two observed p-values, however, depends on whether a non-null treatment effect is or is not present in one of the contrasts. We propose a strategy in which a conservative experiment-wide type I error is achieved by defining the criterion for significance of the smaller observed treatment effect contingent on the magnitude of the larger observed treatment effect. We also discuss sample size requirements for the three-group design.

Drug Evaluation↗
PubMed1989

Long-term efficacy of haloperidol in autistic children: continuous versus discontinuous drug administration.

The aim of this study was to evaluate the long-term efficacy of haloperidol in autistic children and to determine whether discontinuous drug administration was as effective as continuous drug administration. Sixty children, 48 males and 12 females, ages 2.3 to 7.9 years (X 5.1) completed the study. They received haloperidol over a period of 6 months followed by a 4-week drug withdrawal/placebo period. Haloperidol remained effective, and the discontinuous treatment schedule did not diminish its efficacy. Children with prominent symptoms of irritability, angry and labile affect, and uncooperativeness were the best responders to haloperidol.

Autistic Disorder↗
PubMed1989

Naltrexone in autistic children: an acute open dose range tolerance trial.

The safety and efficacy of naltrexone was explored in an open acute dose range tolerance trial in 10 hospitalized autistic children, ages 3.42 to 6.50 years (mean, 5.04). Naltrexone was given in ascending doses: 0.5, 1.0, and 2.0 mg/kg/day. Behavioral side effects were observed as early as 1/2 hour after dosing. Ratings on the Children's Psychiatric Rating Scale showed that withdrawal was reduced across all three dose levels; administration of 0.5 mg/kg/day dose resulted in increased verbal production; and the 2.0 mg/kg/day dose resulted in reduction of sterotypies. Mild sedation of brief duration was the only side effect. Electrocardiogram, liver function tests, and all other laboratory studies remained unchanged throughout the study. These preliminary findings require replication in a larger sample of patients under double-blind and placebo controlled condition.

Autistic Disorder↗
PubMed1989

Efficacy of combinations of intramuscular antipsychotics and sedative-hypnotics for control of psychotic agitation.

The combination of haloperidol, 5 mg, and lorazepam, 4 mg, was both effective and safe for managing agitated behavior in an open trial with acutely psychotic patients. The combination also appeared to be superior to its individual components when studied in a randomized, nonblind trial. The principle of the combined use of antipsychotics and sedative-hypnotics was further tested by comparing two new combinations: thiothixene, 5 mg, and lorazepam, 4 mg, versus haloperidol, 5 mg, and phenobarbital sodium, 130 mg. These combinations had comparable efficacy and safety, and the level of transquilization approached that produced by the haloperidol-lorazepam combination in the preceding studies.

Adolescent↗
PubMed1989

Design issues in clinical trials.

As noted, many issues in the design of clinical trials and the analysis of data therefrom deserve consideration with respect to Alzheimer's disease. This chapter has emphasized the different types of experimental designs that appear most appropriate in different phases of clinical drug development. Intensive within-subject designs that contrast different treatment conditions within the same group of subjects appear useful for early clinical trials. The standard parallel-groups design can provide substantial evidence of short-term efficacy in large-scale, multicenter trials; however, longer term treatment is required to evaluate the practical value of a new drug for the treatment of Alzheimer's disease. A survival analysis model is proposed as useful to ensure only minimal deterioration before termination of double-blind conditions for patients who might be assigned to placebo. Research protocols that plan in advance an interim analysis of data from large-scale clinical trials can be useful in reaching early decisions while not jeopardizing continuation of studies in which no interim decision is justified. A special issue regarding the reporting of two-tail p-values for tests of treatment effects that can only have practical consequences in one direction has been discussed as particularly relevant to FDA evaluation of placebo-controlled clinical trials. One-tail p-values represent the actual Type I error probabilities in cases where treatment effects in only one direction will ever be the basis for a claim of statistical significance.

Alzheimer Disease↗
PubMed1988

An efficacy study of isocarboxazid and placebo in depression, and its relationship to depressive nosology.

Isocarboxazid and placebo were evaluated in 130 anxious depressives. Drug was superior to placebo on depression, anxiety, interpersonal sensitivity, and global measures, and on symptoms of hostility, anxiety, obsessiveness, and psychological-cognitive components of depression. There were no significant differences between treatment effects on psychomotor and typical vegetative symptoms. Isocarboxazid was more effective than placebo in major, but not in minor, depression. It was significantly more effective in depression classified as endogenous depression or melancholia by various diagnostic criteria. Drug was more effective than placebo in atypical depression with vegetative reversal and in Brief Psychiatric Rating Scale (BPRS)-derived profiles of anxious and hostile depression; there were no drug-placebo differences in atypical depression without vegetative reversal, or in BPRS retarded and agitated/excited depression. Interpersonal sensitivity emerged as an important drug-responsive dimension.

Adult↗
PubMed1988

Double-blind comparison of alprazolam, diazepam, and placebo for the treatment of negative schizophrenic symptoms.

Fifty-five schizophrenic outpatients with negative symptoms were treated for up to six weeks by the addition of alprazolam (mean dose, 4.2 mg/d), diazepam (mean dose, 40.4 mg/d), or placebo to their ongoing neuroleptic treatment. A repeated-measures analysis of variance with baseline measurements entered as covariates indicated the presence of a significant time X drug interaction effect for the weekly Brief Psychiatric Rating Scale (BPRS) withdrawal/retardation subfactor scores. During the initial weeks of the study, the alprazolam-treated group had lower scores, while the diazepam-treated group had higher scores than the placebo-treated group. However, an end point analysis performed on the final BPRS withdrawal/retardation subfactor scores showed no significant differences among the three groups, nor were beneficial effects observed on any of the BPRS subfactor scores that assess positive symptoms. Plasma alprazolam levels were maintained throughout the study and ranged from 20 to 100 ng/mL. These results suggest that alprazolam had no sustained significant effect on negative schizophrenic symptoms.

Adult↗
PubMed1988

Accelerated mental aging in alcoholic patients.

Discriminant function and polynomial regression methods were used to define a mental age function from scale score profile patterns found in the WAIS manual. Values on the mental age function then were calculated from WAIS scale score profiles for 164 alcoholics in the age range 35 to 74. Validity of the mental age function was evident in clear discrimination between chronological age groups in the alcoholic sample. As compared with WAIS normative values for the mental age function, the mean mental age for patients in the alcoholic sample was advanced approximately 7 years over age-matched normals. Unweighted means ANOVA revealed the accelerated mental aging of alcoholic patients to be statistically significant. This finding is discussed in the context of other research that supports a premature aging hypothesis.

Adult↗
PubMed1988

DSM-III diagnosis and code types of the Diagnostic Inventory of Personality and Symptoms.

The relationships of high-point code types of the Diagnostic Inventory of Personality and Symptoms (DIPS) to the Diagnostic and Statistic Manual III of the American Psychiatric Association (DSM-III) were explored for patients (N = 316) in private mental health settings. Sixteen DIPS code types that relate code types to Axis I diagnoses are presented. The three DIPS personality disorder cluster scales and the eight combinations thereof are presented as well. Five of the personality disorder cluster scale code types that relate to DSM-III Axis II categories are identified. Finally, a narrative summation of each of the code types is given.

Humans↗
PubMed1988

Behavioral assessment of psychopathology in children: infantile autism.

The utility of a subtest of 14 items from the Children's Psychiatric Rating Scale (CPRS) for evaluating psychopathology in autistic children was examined. A series of 180 autistic children, who satisfied the DSM-III criteria for Infantile Autism, Full Syndrome Present, were rated on the CPRS. A series of children with conduct disorder diagnoses were added to provide a contrast group for investigating specificity of behavioral manifestations with regard to autism. Multivariate analysis was used to elucidate major behavioral dimensions, to identify distinct subtypes, and to evaluate discriminant validity of the CPRS behavioral ratings.

Autistic Disorder↗