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Results for “hypothesis testing”

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At least 127 records · Page 7Linked to original sources
PubMed2003

Delayed-onset hypothesis of antipsychotic action: a hypothesis tested and rejected.

CONTEXT: To understand the mechanism of action of antipsychotic drugs, it is critical to recognize the time course over which these medications take effect. Current models of antipsychotic action presume a "delayed onset" of action. OBJECTIVE: To test the delayed-onset hypothesis of antipsychotic action via a meta-analytic study. DATA SOURCES AND STUDY SELECTION: Double-masked studies that reported results from active or placebo-controlled trials of antipsychotic response during the first 4 weeks of treatment were selected. These studies were identified by searching MEDLINE, 1996 to 2001; the Cumulative Index to Nursing and Allied Health, 1982 to 2001; EMBASE, 1980 to 2001; the ACP Journal Club; the Cochrane Database of Systematic Reviews; and the Database of Abstracts of Reviews of Effectiveness. Leads from these sources were followed up by manual searches. DATA SYNTHESIS: Forty-two published studies, including 7450 patients and 119 independent response vs time curves, were identified. Reductions in total scores on the Brief Psychiatric Rating Scale and the Positive and Negative Syndrome Scale were 13.8% during week 1, 8.1% during week 2, 4.2% during week 3, and 4.7% during week 4. This pattern of "early-onset" improvement was present even after the estimated effect of placebo treatment was removed and when results were restricted to the psychotic subscales of the scales. CONCLUSIONS: This analysis rejects the commonly held hypothesis that antipsychotic response is delayed. Rather, these findings suggest that the antipsychotic response starts in the first week of treatment and accumulates over time. Furthermore, greater improvement occurs in the first 2 treatment weeks than in the subsequent 2 treatment weeks. Proposed mechanisms of action of antipsychotic drugs need to account for this early-onset antipsychotic effect.

Adolescent↗
PubMed2006

SNOOP:a program for demonstrating the consequences of premature and repeated null hypothesis testing.

The ease with which data can be collected and analyzed via personal computer makes it potentially attractive to "peek" at the data before a target sample size is achieved. This tactic might seem appealing because data collection could be stopped early, which would save valuable resources, if a peek revealed a significant effect. Unfortunately, such data snooping comes with a cost. When the null hypothesis is true, the Type I error rate is inflated, sometimes quite substantially. If the null hypothesis is false, premature significance testing leads to inflated estimates of power and effect size. This program provides simulation results for a wide variety of premature and repeated null hypothesis testing scenarios. It gives researchers the ability to know in advance the consequences of data peeking so that appropriate corrective action can be taken.

Computer Simulation↗
PubMed2006

Testing groups of genomic locations for enrichment in disease loci using linkage scan data: a method for hypothesis testing.

Genes for complex disorders have proven hard to find using linkage analysis. The results rarely reach the desired level of significance and researchers often have failed to replicate positive findings. There is, however, a wealth of information from other scientific approaches which enables the formation of hypotheses on groups of genes or genomic regions likely to be enriched in disease loci. Examples include genes belonging to specific pathways or producing proteins interacting with known risk factors, genes that show altered expression levels in patients or even the group of top scoring locations in a linkage study. We show here that this hypothesis of enrichment for disease loci can be tested using genome-wide linkage data, provided that these data are independent from the data used to generate the hypothesis. Our method is based on the fact that non-parametric linkage analyses are expected to show increased scores at each one of the disease loci, although this increase might not rise above the noise of stochastic variation. By using a summary statistic and calculating its empirical significance, we show that enrichment hypotheses can be tested with power higher than the power of the linkage scan data to identify individual loci. Via simulated linkage scans for a number of different models, we gain insight in the interpretation of genome scan results and test the power of our proposed method. We present an application of the method to real data from a late-onset Alzheimer's disease linkage scan as a proof of principle.

Alzheimer Disease↗
PubMed2004

Cell proliferation and apoptosis: dual-signal hypothesis tested in tuberculous pleuritis using mycobacterial antigens.

Antigens and mitogens have the innate ability to trigger cell proliferation and apoptosis thus exhibiting a dual-signal phenomenon. This dual-signal hypothesis was tested with mycobacterial antigens (PPD and heat killed Mycobacterium tuberculosis - MTB) in tuberculous pleuritis patients where the immune response is protective and compartmentalized. We compared and correlated the cell-cycle analysis and antigen-induced apoptosis in normal and patients' peripheral blood mononuclear cells (PBMCs) and patients' pleural fluid mononuclear cells (PFMCs). In cell-cycle analysis, PFMCs showed good mitotic response with PPD and MTB antigens where 10% and 7% of resting cells entered the S and G2/M phases of cell cycle, respectively. This antigen-induced proliferation of PFMCs correlated well with the lymphocyte transformation test (LTT) results. On the other hand, PFMCs also showed 21% of spontaneous apoptosis, which further increased to 43%, by induction with known apoptotic agent like Dexamethasone (DEX) and the mycobacterial antigens PPD and MTB. Further we demonstrated by anti-CD3 induction experiments that prior activation of cells is prerequisite for them to undergo apoptosis. Our results showed that PPD and MTB antigens induced both cell proliferation and apoptosis in PFMCs, which were pre-sensitized to mycobacterial antigens in vivo. Thus the dual-signal phenomenon was operative against these antigens in tuberculous pleuritis. We also demonstrated that the activated cells are more predisposed to apoptosis.

Antibodies, Monoclonal↗
PubMed1998

Do sex hormones play a role in the etiology of esophageal adenocarcinoma? A new hypothesis tested in a population-based cohort of prostate cancer patients.

The striking male predominance in patients with adenocarcinoma of the esophagus (male:female ratio = 6:1) is not explained by known risk factors. We hypothesized that sex hormones could be responsible for this sex imbalance. If the hypothesis is correct, treatment that increases the estrogen level and/or decreases the testosterone level in males might reduce the risk of developing esophageal adenocarcinoma. To test our hypothesis, we performed a population-based, retrospective cohort study among all patients given a diagnosis of prostate cancer in Sweden between 1958 and 1992. The vast majority had received prolonged antiandrogenic treatment, typically with estrogens. A total of 100,215 patients were followed up for an average of 4 years. The standardized incidence ratio, the ratio of the observed to the expected number of incident cancers, was used as a measure of relative risk, with the expected number derived from the entire Swedish population. We observed 14 adenocarcinomas of the esophagus during follow-up in the cohort, compared to the 16 expected, yielding a relative risk close to unity (standardized incidence ratio = 0.9; 95% confidence interval = 0.5-1.5). Analysis by latency intervals after prostate cancer diagnosis revealed no clear trend toward increasing or decreasing risk over time. In conclusion, our Swedish data did not provide any support for our hypothesis of a role of sex hormones in the etiology of esophageal adenocarcinoma.

Adenocarcinoma↗
PubMed2005

Epigenetic hypothesis tests for methylation and acetylation in a triple microarray system.

To fully elucidate the functional relationship between DNA methylation and histone hypoacetylation in gene silencing, we have developed an integrated "triple" microarray system that allows us to begin to decipher the influence of epigenetic hierarchies on the regulation of gene expression in cancer cells. Our hypothesis is that in the promoter region of a silenced gene, reversal of two epigenetic factors (i.e., DNA demethylation and/or histone hyperacetylation) is highly correlated with gene reexpression after treatment of the human epithelial ovarian cancer cell line CP70 with the drug combination 5-aza-2'-deoxycytidine (DAC), a demethylating agent, and trichostatin A (TSA), an inhibitor of histone deacetylases. To estimate the posterior probabilities for genes with altered expression, DNA methylation and histone acetylation status measured with a triple-microarray system, we have employed an established empirical Bayes model. Two methods have been proposed to test our hypothesis that DNA demethylation and histone hyperacetylation are highly correlated among those up-regulated genes. One method follows a weighted least squares regression, while the other is derived from a chi-square statistic. The data derived by these approaches, which have been further verified through bootstrap analyses, support the proposed epigenetic correlation (p-values are less than 0.001). Further simulations suggest that even if the constant variance and normality assumptions do not hold, the power of those two tests is robust.

Acetylation↗
PubMed1984

Clinical hypothesis testing in family practice: a biopsychosocial perspective.

Recent studies of the clinical problem-solving process have demonstrated the importance of hypothesis generation and testing in shaping the nature of information gathering, differential diagnosis, and therapeutic decision making. Family physicians and other primary care physicians are often faced with complex and undifferentiated illness problems that require them to go beyond the traditional biomedical model and entertain an expanded range of psychosocial hypotheses. In this paper the authors draw upon clinically relevant behavioral and social science research and propose several biopsychosocial hypotheses that have proven useful in the management of family practice patients. Seven illustrative case studies are presented, and some implications of this biopsychosocial paradigm for practice, research, and teaching are discussed.

Adolescent↗
PubMed1980

Interpretation of research data: hypothesis testing.

The application of statistical tests to the evaluation of hypotheses is discussed. The statistical test is used to determine whether or not a hypothesis is correct by telling the researcher how likely it is that the results of an experiment are due to chance alone. Generally, a null hypothesis is set up stating that there is no difference between the control and experimental samples. The data are than collected and analyzed, and the null hypothesis is either accepted or rejected. The researcher, before beginning actual experimentation, should establish a level of significance to indicate how certain he wishes to be that the results are not due to chance alone. Traditionally, this level is set at 95% or 99% (expressed as a level of significance of 0.05 or 0.01, respectively). In using these tests, two types of error are possible. The null hypothesis can be rejected when it is in fact true (Type I error), or it can be accepted when it is false (Type II error). Since all statistical tests are based on certain assumptions concerning the data, the test applied to experimental results must be chosen to fit the data (e.g., collection methods, distribution type). for these reasons, statistical tests should be chosen before the experiment, and the experimental procedures should be tailored to fit the statistical test so that the validity of the analysis will be maximized.

Analysis of Variance↗
PubMed1996

Hypothesis testing and earthquake prediction.

Requirements for testing include advance specification of the conditional rate density (probability per unit time, area, and magnitude) or, alternatively, probabilities for specified intervals of time, space, and magnitude. Here I consider testing fully specified hypotheses, with no parameter adjustments or arbitrary decisions allowed during the test period. Because it may take decades to validate prediction methods, it is worthwhile to formulate testable hypotheses carefully in advance. Earthquake prediction generally implies that the probability will be temporarily higher than normal. Such a statement requires knowledge of "normal behavior"--that is, it requires a null hypothesis. Hypotheses can be tested in three ways: (i) by comparing the number of actual earth-quakes to the number predicted, (ii) by comparing the likelihood score of actual earthquakes to the predicted distribution, and (iii) by comparing the likelihood ratio to that of a null hypothesis. The first two tests are purely self-consistency tests, while the third is a direct comparison of two hypotheses. Predictions made without a statement of probability are very difficult to test, and any test must be based on the ratio of earthquakes in and out of the forecast regions.

Journal Article↗
PubMed1994

Efficient use of biological banks for biochemical epidemiology: exploratory hypothesis testing by means of a sequential t-test.

In view of recent advances in molecular and biochemical epidemiology, there is growing interest in the creation of biological banks of blood, urine, tissue, or other biological specimens collected from participants in prospective cohort studies. The existence of biological banks may make it possible to study a multitude of etiologic hypotheses, by comparing biochemical parameters measured in the biological specimens of subjects who will eventually develop the disease of interest ("cases") and of control subjects, using a nested case-control or a case-cohort design. In practice, however, the amount of biological material available per subject (in particular, that of cases) will limit the number of hypotheses that can be tested. The present paper discusses the use of a sequential t-test which, compared with an analogous fixed sample procedure, will on average require fewer biological specimens before a given study hypothesis can be accepted or rejected. The sequential test should thus facilitate an early decision on whether a new hypothesis is worth further investigation, while avoiding wasting too much biological material on testing hypotheses that may eventually prove unfruitful. If the test reveals an exposure difference of interest, the study may be extended so that relevant epidemiologic effect measures can be estimated more accurately.

Biological Specimen Banks↗
PubMed1997

Hypothesis testing and effect size estimation in clinical trials.

LEARNING OBJECTIVES: This paper provides the reader with an overview of several key elements in study planning and analysis. In particular, it highlights the differences between significance tests (statistical significance) and effect size estimation (clinical significance). DATA SOURCES: This paper focuses on methodologic issues, and provides an overview of trends in research. PAPER SELECTION: References were selected to provide a cross-section of the approaches currently being used. The paper also discusses a number of logical fallacies that have been cited as examples in earlier papers on research design. CONCLUSIONS: Significance tests are intended solely to address the viability of the null hypothesis that a treatment has no effect, and not to estimate the magnitude of the treatment effect. Researchers are advised to move away from significance tests and to present instead an estimate of effect size bounded by confidence intervals. This approach incorporates all the information normally included in a test of significance but in a format that highlights the element of interest (clinical significance rather than statistical significance). This approach should also have an impact on study planning--a study should have enough power to reject the null hypothesis and also to yield a precise estimate of the treatment effect.

Clinical Trials as Topic↗
PubMed1976

The psychiatric examination in the walk-in clinic. Hypothesis generation and hypothesis testing.

Rapid assessment for decision making is a major goal of the initial psychiatric interview in walk-in clinics, emergency psychiatric services, and the ambulatory services of community mental health centers. To accomplish this task, the clinician must learn to elicit specific data to confirm or refute clinical hypotheses rather than gather a complete history. This report, in formulating a hypothesis generating and testing approach for the initial psychiatric examination, proposes 16 hypotheses that organize the clinical data necessary for most decisions. This approach is intended to help the clinician make efficient use of limited time, guard him from coming to premature closure in the collection of data, and provide a stimulus for the exploration of relevant but neglected clinical questions.

Affective Symptoms↗
PubMed2005

Investigating the evolutionary history of the Pacific Northwest mesic forest ecosystem: hypothesis testing within a comparative phylogeographic framework.

We examine the evolution of mesic forest ecosystems in the Pacific Northwest of North America using a statistical phylogeography approach in four animal and two plant lineages. Three a priori hypotheses, which explain the disjunction in the mesic forest ecosystem with either recent dispersal or ancient vicariance, are tested with phylogenetic and coalescent methods. We find strong support in three amphibian lineages (Ascaphus spp., and Dicampton spp., and Plethodon vandykei and P. idahoensis) for deep divergence between coastal and inland populations, as predicted by the ancient vicariance hypothesis. Unlike the amphibians, the disjunction in other Pacific Northwest lineages is likely due to recent dispersal along a northern route. Topological and population divergence tests support the northern dispersal hypothesis in the water vole (Microtus richardsoni) and northern dispersal has some support in both the dusky willow (Salix melanopsis) and whitebark pine (Pinus albicaulis). These analyses demonstrate that genetic data sampled from across an ecosystem can provide insight into the evolution of ecological communities and suggest that the advantages of a statistical phylogeographic approach are most pronounced in comparisons across multiple taxa in a particular ecosystem. Genetic patterns in organisms as diverse as willows and salamanders can be used to test general regional hypotheses, providing a consistent metric for comparison among members of an ecosystem with disparate life-history traits.

Amphibians↗
PubMed2005

Early-onset hypothesis of antipsychotic drug action: a hypothesis tested, confirmed and extended.

BACKGROUND: A recent meta-analysis rejected the "delayed onset of antipsychotic action hypothesis" that had been described in textbooks for decades. Since meta-analyses are prone to a number of methodological problems, we attempted a replication by a) using a large database of individual patient data rather than meta-analysis, b) including another antipsychotic and c) extending the analysis from four weeks to one year. METHODS: We pooled the data of seven randomized trials involving amisulpride. The data included 1708 patients with schizophrenia and positive symptoms and we examined the incremental percentage Brief Psychiatric Rating Scale (BPRS) reduction over time. RESULTS: The "early onset of antipsychotic action hypothesis" was confirmed, as the reduction of overall and positive symptoms until week two was larger than the additional reduction until week four (p<.0001). Furthermore, in a subset with long-term data (n=748) approximately 68% of the mean BPRS change at one year was already achieved at four weeks in the observed cases. CONCLUSIONS: A substantial amount of the antipsychotic drug effect seems to occur during the first weeks of treatment. Subsequent analyses are needed to establish how long an antipsychotic should be tried before it is considered ineffective and alternative strategies implemented.

Amisulpride↗
PubMed1990

Tracing the footsteps of Sherlock Holmes: cognitive representations of hypothesis testing.

A well-documented phenomenon in opinion-revision literature is subjects' failure to revise probability estimates for an exhaustive set of mutually exclusive hypotheses in a complementary manner. However, prior research has not addressed the question of whether such behavior simply represents a misunderstanding of mathematical rules, or whether it is a consequence of a cognitive representation of hypotheses that is at odds with the Bayesian notion of a set relationship. Two alternatives to the Bayesian representation, a belief system (Shafer, 1976) and a system of independent hypotheses, were proposed, and three experiments were conducted to examine cognitive representations of hypothesis sets in the testing of multiple competing hypotheses. Subjects were given brief murder mysteries to solve and allowed to request various types of information about the suspects; after having received each new piece of information, subjects rated each suspect's probability of being the murderer. Presence and timing of suspect eliminations were varied in the first two experiments; the final experiment involved the varying of percentages of clues that referred to more than one suspect (for example, all of the female suspects). The noncomplementarity of opinion revisions remained a strong phenomenon in all conditions. Information-search data refuted the idea that subjects represented hypotheses as a Bayesian set; further study of the independent hypotheses theory and Shaferian belief functions as descriptive models is encouraged.

Adult↗
PubMed1996

The force requirements for tooth movement. Part III: The pressure hypothesis tested.

Many experiments have investigated the force requirements for tooth movement; the diverse results so obtained have lead to controversy and resulted in an incomplete understanding of the true nature of tooth movement. This study analyses the results of two experiments which investigated the relation between the force applied and the rate of tooth movement from the standpoint of the pressures exerted by the tooth root on the surrounding tooth-periodontal membrane complex. The pressure hypothesis suggested by Smith and Storey is tested using the estimated projected area of the teeth moved in the experiments as a means of calculating the estimated pressures resulting from the application of orthodontic forces. The average pressure at which optimal rates of tooth movement occurred in these experiments was 197 gf cm-2.

Adolescent↗
PubMed2002

Implicit and explicit processes in a hypothesis testing task.

We present the results of two experiments investigating the factors that determine responding on the pseudo-diagnosticity task. In Expt 1 we manipulated people's beliefs about the degree to which an initial piece of evidence supported a focal hypothesis and found decreased pseudo-diagnostic (PD) responding when the evidence offered low support for the focal hypothesis. In Expt 2 we manipulated the instructions given to participants. We found that instructions to select evidence to help decide between the focal and the complementary hypotheses produced fewer PD responses than both instructions to decide whether the focal hypothesis was the case and instructions to decide whether its complement was the case. The results are interpreted within the framework of recent dual process theories of reasoning.

Adolescent↗