Statistical significance testing and clinical trials.

The efficacy of treatments is better expressed for clinical purposes in terms of these treatments' outcome distributions and their overlapping rather than in terms of the statistical significance of these distributions' mean differences, because clinical practice is primarily concerned with the outcome of each individual client rather than with the mean of the variety of outcomes in any group of clients. Reports of the obtained outcome distributions for the comparison groups of all competently designed and executed randomized clinical trials should be publicly available no matter what the statistical significance of the mean differences among these groups, because all of these studies' outcome distributions provide clinically useful information about the efficacy of the treatments compared. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Comparing several robust tests of stochastic equality with ordinally scaled variables and small to moderate sized samples.

In a comparison of 2 treatments, if outcome scores are denoted by X in 1 condition and by Y in the other, stochastic equality is defined as P(X = P(X > Y). Tests of stochastic equality can be affected by characteristics of the distributions being compared, such as heterogeneity of variance. Thus, various robust tests of stochastic equality have been proposed and are evaluated here using a Monte Carlo study with sample sizes ranging from 10 to 30. Three robust tests are identified that perform well in Type I error rates and power except when extremely skewed data co-occur with very small n. When tests of stochastic equality might be preferred to tests of means is also considered. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Improving the relationship between the randomized clinical trial and real-world clinical practice.

I comment on the article by Krause (see record 2011-19228-002), which discusses a number of ways for clinical psychotherapy outcome researchers to make the results of randomized controlled trials (RCT) more useful to practicing psychotherapists primarily by making the distributions of raw data from those studies available to the public. In this way, it would be possible for psychotherapists to determine which treatment of an RCT (experimental or control) would be best for a specific patient. Problems with this proposal are discussed and an alternative model that integrates psychotherapy outcome data from group means and clinical case studies is offered. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Limitations of the dodo bird verdict and the role of clinical trials in psychotherapy research: Comment on Wampold et al. (1997).

B. E. Wampold et al.'s (1997) meta-analysis provides a useful and methodologically sophisticated summary of the results of comparative psychotherapy outcome research. Despite its strengths, some limitations of the meta-analysis that may have biased the results against finding differences between treatments are pointed out in this article. In addition, the types of treatments and patient populations to which the results can be generalized are clarified through an analysis of the studies contained within the meta-analysis. The importance of exceptions to the Dodo bird verdict is emphasized. Disagreements with Wampold et al. on the implications of the their meta-analysis for research and practice, in particular the role of clinical trials in psychotherapy research and the need for identifying treatments that are "empirically supported," are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Common methodological problems in research on the addictions.

Among the common methodological problems in research on the addictions are (a) selective, incomplete, or biased reviews of prior research; (b) reliance on inadequate or incomplete diagnostic criteria in choosing Ss; (c) choice of inappropriate comparison groups; (d) use of inadequate alcoholic analogs when alcoholic Ss are unavailable; (e) failure to adequately account for treatment dropouts; (f) unwarranted choice of single-S over group designs and vice versa; (g) failure to ensure that comparably trained, equivalently committed therapists provide both experimental and control treatments; (h) failure to ensure that patients in both experimental and control treatments receive treatments as therapist- and time-intensive; (i) failure to follow patients for adequate lengths of time posttreatment; (j) failure to provide for adequate, multidimensional treatment outcome measures tapping a full range of patient behavior; (k) failure to exercise restraint, scientific modesty, and criticality in reporting results of one's own research; and (l) failure to recognize differences between statistical and clinical significance. (39 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A molecular perspective of the genetic relationships of G-protein coupled melatonin receptor subtypes

OBJECTIVE: To compare the efficacy, tolerance and recurrence rate of endometriosis after 5-year follow-up of treatment with Gestrinone and Buserelin, respectively. STUDY DESIGN: A prospective study with randomized follow-up of 5 years duration (minimum) for each patient was done. We included 43 cases of endometriosis diagnosed by laparoscopy or laparotomy and treated them with Gestrinone (Group G, n = 25 cases) or Buserelin intranasal spray (Group B, n = 18) for 6 months. RESULTS: General data: Age, height, weight of patients and AFS score of endometriosis were without significant differences in either group. Specific data: A) Global clinical efficacy was good or excellent in 74% (16/25) of group G and in 78% (14/18) of group B without significant differences. B) Global clinical tolerance was good in 50% of the patients in group G and in 0% in group B (p < 0.001). C) Global evaluation after 5-year follow-up showed "success" only for 36% of patients in group G and in 33% in group B (no significant differences), with "failure" in 40% and 33%, respectively (no significant differences). CONCLUSIONS: 1) Gestrinone and Buserelin intranasal spray are valid treatments for the remission of endometriosis, with "success", "failure" and "clinical recurrence" rates similar after a follow-up of 5 years of initial treatment. 2) The most significant androgenic effect of Gestrinone was the presence of acne. Vascular effects were also considered as very undesirable effects according to the comments of patients. On the contrary, the effects of analogs are generally better tolerated.     

Effectiveness of behavioral therapy for chronic low back pain: A component analysis.

The effects of outpatient group behavioral therapy including aerobic exercise (BE), behavioral therapy only (B), and aerobic exercise only (E) on pain and physical and psychosocial disability were evaluated and compared in a group of mildy disabled chronic low-back-pain patients. Ninety-six Ss were randomly assigned to the 3 treatments and a waiting-list control (WL) condition and assessed on a variety of patient self-report, spouse-rated, and direct observational measures at pretreatment, posttreatment, and 6- and 12-month follow-ups. Patients in the BE condition, but not the B or E conditions, improved significantly more pretreatment to posttreatment than did WL patients on the patient self-report and observer-rated measures. At both follow-ups, all 3 treatment groups remained significantly improved from pretreatment, with no significant differences among treatments. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Goal consensus and collaboration.

There are differences in the extent to which patient and therapist agree on psychotherapy goals and work together in the helping relationship. This article reviews the empirical research on the relation between psychotherapy outcome and patient-therapist goal consensus and collaboration. Research results suggest that psychotherapy outcome is enhanced when agreement on therapeutic goals and collaborative involvement (often assessed by patient cooperation, role involvement, and homework compliance) are present during the course of therapy. When therapists and patients demonstrate cooperative and affiliative behavior, and when patients are actively involved in the patient role, better outcomes can be expected. We discuss therapeutic practices based on these findings, emphasizing the involvement of therapist and patient in a process of shared decision-making where goals are frequently discussed and agreed upon. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Discriminant validation of an MMPI measure of aggression.

An MMPI measure of aggression formed by summing scales F (Frequency), 4 (Psychopathic Deviate), and 9 (Hypomania) discriminated 3 groups of neuropsychiatric outpatients (N?=?138) defined by qualitative and quantitative differences in violent behavior. Results indicate that the group differences cannot be attributed to differences in more general factors such as age, sex, education, IQ, or degree of overall psychopathology, reflecting favorably on the measure's discriminant validity. However, there was sufficient overlap among the distributions of groups to call its clinical utility into question. Further research appears to be needed in order to better define what this scale measures as well as its range of applicability. (5 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Synaptic proteins of the temporal associative area of the neocortex of cats (field Ep) with normal and reduced cognitive capacities

Genetically hypercholesterolaemic RICO rats (male, 6 weeks old) were randomly distributed into 6 experimental groups. The zero-time basal group A was sacrificed at the start of the experiment while the other groups were fed for 6 weeks and then sacrificed. Group B was fed a stock diet. Control group C was fed a high-sucrose (45%) diet with 0.5% added cholesterol. In the diet of group D, only the magnesium (Mg) content was reduced from the level of group C (883 ppm) to 200 ppm. The diet of group E was the same as that of group D with the addition of 12 ppm of fluoride (F) and the diet of group G was the same as that of group E, but with its Mg content elevated from 200 ppm to 300 ppm. Analysis of aortic blood samples, taken before sacrifice, indicated significant increases in total serum cholesterol (p < 0.01), very low density lipoprotein (VLDL) (p < 0.001) and low density lipoprotein (LDL), (p < 0.001) cholesterol, and a trend to lower high density lipoprotein (HDL) cholesterol in group C, as compared to group B. Significantly lower total (p < 0.05), VLDL (p < 0.01) and LDL (p < 0.01) triglycerides were observed in group C when compared to group B. The LDL phospholipids were significantly higher in group C (p < 0.001) than in group B. When cholesterol levels in groups D, E and G were compared with group C, the VLDL cholesterol in group E and the LDL cholesterol in group G were slightly but significantly (p < 0.05) reduced, while total cholesterol and the other subfractions were unaltered. The LDL triglycerides of groups E and G were significantly smaller still than the already small fraction in group C. The VLDL triglyceride in group E was significantly lower than that of group C (35% reduction, p < 0.001), D and G (p < 0.05). Phospholipids were slightly but significantly reduced in the VLDL fraction of group E and in the LDL fraction of group G (p < 0.05 and 0.01, respectively), as compared to those of group C.     

Urinary C5b-9 excretion and clinical course in idiopathic human membranous nephropathy

Recent reports suggested that the presence of terminal complement complex (C5b-9) in urine from patients with idiopathic membranous nephropathy (IMN) may indicate on-going immunological damage. This report documents the relationship between C5b-9 excretion and clinical outcome in 35 adult patients with biopsy-proven IMN and progressively declining renal function. There were two groups of patients. Group I received one of three treatment regimens: prednisolone alone, prednisolone and chlorambucil, or prednisolone and cyclophosphamide (N = 22). Group II received no immunosuppressive therapy (N = 17). Three of the 18 patients receiving immunosuppressive drugs had more than one treatment regimen as they experienced a clinical relapse during the study period; hence 22 treatments were available for analysis. Urine samples were collected regularly and urinary C5b-9 (uC5b-9) was determined by ELISA. Both groups were similar with respect to age, sex distribution, and the duration of follow-up. An improvement in proteinuria and creatinine clearance was noted in the immunosuppressed group. Thirty-five patients were excreting C5b-9 initially (18 from group I and 17 from group II); 17 patients continued to excrete C5b-9 at the end of the observation period. These 17 patients had a significantly worse clinical outcome when compared to the 18 patients whose C5b-9 excretion became negative, either spontaneously or with treatment (P < 0.005). These results indicate that continuing C5b-9 excretion is correlated with a poor clinical outcome. They also suggest that uC5b-9 is a dynamic marker of ongoing immunological injury, and therefore may be useful in the initial assessment and monitoring of patients with IMN and in identifying patients who may derive benefit from immunosuppressive therapy.     

Power to detect differences between alternative treatments in comparative psychotherapy outcome research.

Comparative studies of psychotherapy often find few or no differences in the outcomes that alternative treatments produce. Although these findings may reflect the comparability of alternative treatments, studies are often not sufficiently powerful to detect the sorts of effect sizes likely to be found when two or more treatments are contrasted. The present survey evaluated the power of psychotherapy outcome studies to detect differences for contrasts of two or more treatments and treatment vs no-treatment. 85 outcome studies were drawn from 9 journals over a 3-yr period (1984–1986). Data in each article were examined first to provide estimates of effect sizes and then to evaluate statistical power at posttreatment and follow-up. Findings indicate that the power of studies to detect differences between treatment and no treatment is quite adequate given the large effect sizes usually evident for this comparison. However, the power is relatively weak to detect the small-to-medium effect sizes likely to be evident when alternative treatments are contrasted. Thus, the equivalent outcomes that treatments produce may be due to the relatively weak power of the tests. Implications for interpreting outcome studies and for designing comparative studies are highlighted. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A median-based test under informative dropout: the one-sample case

We consider a clinical trial in which the outcome can be assessed by a continuous measure and where dropouts tend to have poorer efficacy than completers. When each subject can act as his/her own control, efficacy is measured by the difference between the outcome measurements at two times. When all subjects complete the protocol, a paired t-test can be used to test for a treatment effect, i.e., whether or not the mean difference is zero. When a patient does not return for the final evaluation, a measure of efficacy cannot be computed for that subject. Often, data from dropouts are ignored and only the observed pairs are used to analyze the data. When the reason for dropping out is not random, the result may be misleading. In this paper, we assume that (1) the distribution of the measure of efficacy (i.e., the change between two outcome measurements) is Gaussian, (2) dropouts would have worse efficacy than the median if they were observed, and (3) the dropout rate is less than 50%. We propose a median-based t-like statistic using the sample median in place of the sample mean. The variance of the median is estimated using only data from the complete half-sample, i.e., the half-sample with better efficacy. Simulations under five patterns of dropouts are performed to compare the proposed statistic with the paired t-test. The results show that the median-based statistic provides a conservative bound for the test of significance of the treatment. In contrast, because the paired t-test does not preserve its level of significance, except when the dropout mechanism is uniform, the paired t-test should not be used for trials in which dropouts tend to have poorer efficacy than completers.     

Therapeutic effort, treatment outcome, and national health policy.

Contends that psychotherapy is seen as repairing or preventing emotional, social, and behavioral dysfunction. The therapeutic effort in the delivery of psychotherapy can be construed as containing 3 components: (1) the dosage of each element in the therapeutic effort; (2) the extent to which each therapeutic intervention restricts the patient's life; and (3) the cumulative costs, in terms of human and material resources invested, of the clinical episode. Dosage measures provide a means of assessing the differences in outcome that might result when 2 or more interventions are provided with the same dosage, or when the same intervention is provided at different dosage levels. Restrictiveness measures provide a means for assessing the differences in outcome that might result when 2 or more interventions seek to control the therapeutic environment in different ways. Cost measures can combine the issues raised in both dosage and restrictiveness studies to provide measures of their combined influences. (23 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Kinds of patients

The basic goal of health outcomes research is to identify the kinds of patients who do (or do not) benefit substantially from specified medical or surgical treatments and procedures. Similarly, clinicians must determine whether particular patients are the kinds of patients who do (or do not) benefit from specified interventions. Such a kinds-based approach to clinical practice is often resisted, however, when physicians are asked to standardize their practices based on the results of health outcome data. In such settings, clinicians often assert that "every patient is unique". The present paper explores the coherence of this claim. In particular, I examine the applicability of the philosophical notion of natural kinds to a kinds-based approach to clinical research and practice. I conclude that the claim of patient uniqueness is misguided. Two key difficulties with a kinds-based approach are examined: the problems associated with (1) assigning single-case probabilities and (2) stereotyping and discrimination.     

Optimal sampling strategies for validation studies.

In selection instrument validation studies the situation occasionally arises in which there are a large number of observations on the predictor but criterion data are very expensive or difficult to obtain, thus making it necessary to sample values of the predictor. Three strategies (random, rectangular, and extreme groups) for sampling predictor values were compared with respect to accuracy and statistical power in estimating the total group validity. Comparisons were made on samples drawn from 6 large N (approximately 10,000) bivariate test score distributions known to contain some departures from linearity and homoscedasticity. It was shown that in this situation selecting values of the predictor that form a rectangular distribution gave, in all instances studied, at least equal accuracy and greater statistical power in estimating the total group validity compared with random sampling. When the predictor–criterion relationship was generally linear with only modest departures from linearity, selecting values from the extremes of the predictor distribution was optimal in terms of accuracy and statistical power and clearly superior to rectangular sampling. (14 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reinforced Variability in Animals and People: Implications for Adaptive Action.

Although reinforcement often leads to repetitive, even stereotyped responding, that is not a necessary outcome. When it depends on variations, reinforcement results in responding that is diverse, novel, indeed unpredictable, with distributions sometimes approaching those of a random process. This article reviews evidence for the powerful and precise control by reinforcement over behavioral variability, evidence obtained from human and animal-model studies, and implications of such control. For example, reinforcement of variability facilitates learning of complex new responses, aids problem solving, and may contribute to creativity. Depression and autism are characterized by abnormally repetitive behaviors, but individuals afflicted with such psychopathologies can learn to vary their behaviors when reinforced for so doing. And reinforced variability may help to solve a basic puzzle concerning the nature of voluntary action. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The interpretation of scores from the EORTC quality of life questionnaire QLQ-C30

While quality of life (QOL) assessment is becoming more common, interpreting the results remains problematic. This paper demonstrates an approach to developing clinically-based interpretations for QOL outcomes, using the QLQ-C30 as an example. The results from 14 published QLQ-C30 studies which group patients by performance status, weight loss, toxicity, extent or severity of disease are collated. Groups with lower clinical status generally have worse QOL. The largest differences are between performance status groups, and the smallest differences are between groups of patients with local disease and those with metastases. The physical and role scores have the largest ranges of means across patient groups, and show the largest differences between clinical groups, while the cognitive and emotional scores have the smallest ranges of means and differences. Sicker groups have larger score standard deviations than healthier groups. Relatively large and small means and differences, and corresponding effect sizes, are presented. Collectively, the results provide a sense of the relative sizes of means and of differences, and of the types of clinical groups which give rise to them, thereby providing clinically-based benchmarks by which to interpret QLQ-C30 results.