|P.Mean: Abstracts for teaching about p-values and confidence intervals (created 2011-12-08).
News: Sign up for "The Monthly Mean," the newsletter that dares to call itself average, www.pmean.com/news.
I am giving a webinar to a group that is interested in applications of statistics to Alzheimer's disease and schizophrenia. I wanted to show some real world uses of p-values and confidence intervals, and did a few quick searches for open source articles. I also am including the abstracts of several articles that they sent me. The font size on the handout is a bit small, so I am including the abstracts here as well so you can view them with a reasonable font size. You can find the handout for this webinar at
This abstract appears on slide #16. Journal article: Bengt Winblad, Jeffrey Cummings, Niels Andreasen, George Grossberg, Marco Onofrj, Carl Sadowsky, Stefanie Zechner, Jennifer Nagel, Roger Lane. A six‐month double‐blind, randomized, placebo‐controlled study of a transdermal patch in Alzheimer's disease–– rivastigmine patch versus capsule International Journal of Geriatric Psychiatry. 2007;22(5):456-467. Abstract: "Objectives: To compare the efficacy, safety and tolerability of a novel rivastigmine transdermal patch with conventional rivastigmine capsules and placebo in patients with Alzheimer's disease (AD). Methods: In this 24-week, multicenter, double-blind, double-dummy, placebo- and active-controlled trial, patients with probable AD were randomized to one of four treatment groups: 12 mg/day rivastigmine capsules; 10 cm2 (9.5 mg/24 h) rivastigmine patch; 20 cm2 (17.4 mg/24 h) rivastigmine patch; or placebo. Primary efficacy measures were the Alzheimer's Disease Assessment Scale—Cognitive subscale (ADAS-Cog) and Alzheimer's Disease Cooperative Study––Clinical Global Impression of Change (ADCS-CGIC). Results: One thousand one hundred and ninety five AD patients from 21 countries participated in the study. Treatment differences (vs placebo) on the ADAS-Cog at Week 24 in 10 cm2 patch, 20 cm2 patch and capsule groups were 1.6 (p = 0.005), 2.6 (p < 0.001) and 1.6 (p = 0.003). Treatment differences on the ADCS-CGIC were 0.3 (p = 0.01), 0.2 (p = 0.054) and 0.3 (p = 0.009). Comparison between the 10 cm2 patch and the capsule revealed non-inferiority. Rates of nausea in the 10 cm2 patch and capsule groups were 7.2% and 23.1%, respectively; rates of vomiting were 6.2% and 17.0%, respectively. Moderate or severe skin irritation occurred in <= 10% patients across the four patch sizes (5, 10, 15 and 20 cm2). Conclusions: The target dose of 10 cm2 rivastigmine patch provides efficacy similar to the highest doses of capsules with a superior tolerability profile. The transdermal patch with rivastigmine may offer convenience important to many caregivers and patients. Keywords: Alzheimer's disease; patch; rivastigmine; transdermal" [Accessed on December 8, 2011]. http://onlinelibrary.wiley.com/doi/10.1002/gps.1788/abstract.
This abstract appears on slide #17 and slide #33. Journal article: Jacqueline A Vernarelli, J Scott Roberts, Susan Hiraki, Clara A Chen, L Adrienne Cupples, Robert C Green. Effect of Alzheimer disease genetic risk disclosure on dietary supplement use Am. J. Clin. Nutr. 2010;91(5):1402-1407. Abstract: "BACKGROUND: Genetic susceptibility testing for Alzheimer disease (AD) with APOE genotype disclosure is not recommended for clinical use but is available through direct-to-consumer (DTC) genetic testing companies. Little is known about whether APOE genotype disclosure would actually prompt changes in nutrition behaviors among at-risk individuals. OBJECTIVE: We studied the effect of APOE genotype disclosure for AD risk assessment on dietary supplement use in adults with a family history of AD. DESIGN: As part of a secondary analysis of data from the second Risk Evaluation and Education for Alzheimer's Disease Study, we examined the effect of genotype disclosure on health-behavior changes among 272 unaffected first-degree relatives of persons with AD. RESULTS: Overall, 16% of all participants reported a change in dietary supplement use after AD risk assessment. Participants who learned that they had at least one copy of the risk-increasing epsilon4 allele (epsilon4+) had 4.75 times the odds of reporting a change in dietary supplement use than did their counterparts who had an absence of the risk-increasing epsilon4 allele (epsilon4-) (95% CI: 2.23, 10.10; P < 0.0001) after adjustment for age, sex, race, baseline supplement use, randomization arm, and educational level. There were no significant differences between APOE epsilon4+ and epsilon4- participants in changes in overall diet, exercise, or medications. CONCLUSIONS: In this sample of first-degree relatives receiving genetic susceptibility testing for AD, an APOE epsilon4+ genotype status was positively associated with dietary supplement use after risk disclosure. Such changes occurred despite the absence of evidence that supplement use reduces the risk of AD. Given the expansion of DTC genetic tests, this study highlights the need for future studies in disease risk communication." [Accessed on December 8, 2011]. http://www.ncbi.nlm.nih.gov/pubmed/20219963.
This abstract appears on slide #18 and slide #34. Journal article: Paul B Rosenberg, Lea T Drye, Barbara K Martin, Constantine Frangakis, Jacobo E Mintzer, Daniel Weintraub, Anton P Porsteinsson, Lon S Schneider, Peter V Rabins, et al. Sertraline for the treatment of depression in Alzheimer disease Am J Geriatr Psychiatry. 2010;18(2):136-145. Abstract: "OBJECTIVE: Depression is common in Alzheimer disease (AD), and antidepressants are commonly used for its treatment, however, evidence for antidepressant efficacy in this population is lacking. The authors conducted a multicenter, randomized, placebo-controlled trial titled "Depression in Alzheimer's Disease-2" to assess the efficacy and tolerability of sertraline for depression in AD. METHODS: One hundred thirty-one participants from five U.S. medical centers with mild-to-moderate AD (Mini-Mental State Examination scores 10-26) and depression of AD were randomized to double-blinded treatment with sertraline (N = 67) or placebo (N = 64), with a target dosage of 100 mg daily. Efficacy was assessed using logistic regressions and mixed effects models in an intention-to-treat analysis with imputation of missing data. Principal outcome measures were modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC), change in Cornell Scale for Depression in Dementia (CSDD) scores, and remission defined by both mADCS-CGIC score <= 2 and CSDD score <= 6. RESULTS: mADCS-CGIC ratings (odd ratio [OR = 1.01], 95% confidence interval [CI]: 0.52-1.97, p = 0.98), CSDD scores (median difference at 12 weeks 1.2, 95% CI: 1.65-4.05, p = 0.41), and remission at 12 weeks of follow-up (OR = 2.06, 95% CI: 0.84-5.04, p = 0.11) did not differ between sertraline (N = 67) and placebo (N = 64). Sertraline-treated patients experienced more adverse events, most notably gastrointestinal and respiratory, than placebo-treated patients. CONCLUSION: Sertraline did not demonstrate efficacy for the treatment depression symptoms in patients with AD. In addition, its use was associated with an increased incidence of adverse events. Thus, selective serotonin reuptake inhibitors may be of limited value for treating depression in patients with AD." [Accessed on December 8, 2011]. http://www.ncbi.nlm.nih.gov/pubmed/20087081.
This abstract appears on slide #35. Journal article: Daniel Weintraub, Paul B Rosenberg, Lea T Drye, Barbara K Martin, Constantine Frangakis, Jacobo E Mintzer, Anton P Porsteinsson, Lon S Schneider, Peter V Rabins, et al. Sertraline for the treatment of depression in Alzheimer disease: week-24 outcomes Am J Geriatr Psychiatry. 2010;18(4):332-340. Abstract: "BACKGROUND: Depression and antidepressant use are common in Alzheimer disease (AD), but the effect of antidepressant treatment for depression on longer term outcomes is unknown. The authors report the Week-24 outcomes of patients who participated in a 12-week efficacy study of sertraline for depression of AD. METHODS: One hundred thirty-one participants (sertraline = 67, placebo = 64) with mild-moderate AD and depression participated in the study. Patients who showed improvement on the modified Alzheimer's Disease Cooperative Study Clinical Global Impression-Change (mADCS-CGIC) after 12 weeks of randomized treatment with sertraline or placebo continued double-blinded treatment for an additional 12 weeks. Depression response and remission at 24 weeks were based on mADCS-CGIC score and change in Cornell Scale for Depression in Dementia (CSDD) score. Secondary outcome measures included time to remission, nonmood neuropsychiatric symptoms, global cognition, function, and quality of life. RESULTS: One hundred seventeen (89.3%) participants completed all study assessments and 74 (56.5%; sertraline = 38, placebo = 36) completed all 24 weeks on randomized treatment. By 24 weeks, there were no between-group differences in depression response (sertraline = 44.8%, placebo = 35.9%; odds ratio [95% CI] = 1.23 [0.64-2.35]), change in CSDD score (median difference = 0.6 [95% CI: -2.26 to 3.46], chi2 [df = 2] = 1.03), remission rates (sertraline = 32.8%, placebo = 21.8%; odds ratio [95% CI] = 1.61 [0.70-3.68]), or secondary outcomes. Common selective serotonin reuptake inhibitor-associated adverse events, specifically diarrhea, dizziness, and dry mouth, and pulmonary serious adverse events were more frequent in sertraline-randomized patients than in placebo subjects. CONCLUSIONS: Sertraline treatment is not associated with delayed improvement between 12 and 24 weeks of treatment and may not be indicated for the treatment of depression of AD." [Accessed on December 8, 2011]. http://www.ncbi.nlm.nih.gov/pubmed/20220589.
The remaining abstracts were not used for the webinar, but I am keeping them here ready for possible future use in a different webinar.
Journal article: Jimmi Nielsen, Søren Skadhede, Christoph U Correll. Antipsychotics associated with the development of type 2 diabetes in antipsychotic-naïve schizophrenia patients Neuropsychopharmacology. 2010;35(9):1997-2004. Abstract: "Diabetes mellitus occurs in schizophrenia patients at higher rates than in the general population. Reasons for this elevated risk are poorly understood and have not been examined prospectively in antipsychotic-naïve, first-episode patients. This study aims to determine which antipsychotics are associated with diabetes development in antipsychotic-naïve schizophrenia patients. All antipsychotic-naïve patients diagnosed with schizophrenia in Denmark between 01 January 1997 and 31 December 2004, followed until 31 December 2007, allowing for >=3 years follow-up, unless death or diabetes onset occurred. Risk factors for the time to diabetes onset were assessed, including antipsychotics taken for at least 180 defined daily doses in the first year after first antipsychotic prescription ('initial treatment'). Risk factors for diabetes incidence were assessed, including antipsychotic use within 3 months before diabetes onset or study end ('current treatment'). Of 7139 patients, followed for 6.6 years (47,297 patient years), 307 developed diabetes (annual incidence rate: 0.65%). Time to diabetes onset was significantly shorter in patients with higher age (hazard ratio (HR): 1.03, confidence interval (CI): 1.02-1.03) and those with 'initial' treatment of olanzapine (HR: 1.41, CI: 1.09-1.83), mid-potency first-generation antipsychotics (FGAs) (HR: 1.60, CI: 1.07-2.39), antihypertensive (HR: 1.87, CI: 1.13-3.09), or lipid-lowering drugs (HR: 4.67, CI: 2.19-10.00). Significant factors associated with diabetes within 3 month of its development included treatment with low-potency FGAs (odds ratio (OR): 1.52, CI: 1.14-2.02), olanzapine (OR: 1.44, CI: 1.98-1.91), and clozapine (OR: 1.67, CI: 1.14-2.46), whereas aripiprazole was associated with lower diabetes risk (OR: 0.51, CI: 0.33-0.80). In addition to general diabetes risk factors, such as age, hypertension, and dyslipidemia, diabetes is promoted in schizophrenia patients by initial and current treatment with olanzapine and mid-potency FGAs, as well as by current treatment with or low-potency first-generation antipsychotics and clozapine, whereas current aripiprazole treatment reduced diabetes risk. Patients discontinuing olanzapine or mid-potency FGA had no increased risk of diabetes compared with patient not treated with the drugs at anytime." [Accessed on December 8, 2011]. http://www.ncbi.nlm.nih.gov/pubmed/20520598.
Journal article: Solomon Teferra, Teshome Shibre, Abebaw Fekadu, Girmay Medhin, Asfaw Wakwoya, Atalay Alem, Gunnar Kullgren, Lars Jacobsson. Five-year mortality in a cohort of people with schizophrenia in Ethiopia BMC Psychiatry. 2011;11:165. Abstract: "BACKGROUND: Schizophrenia is associated with a two to three fold excess mortality. Both natural and unnatural causes were reported. However, there is dearth of evidence from low and middle income (LAMIC) countries, particularly in Africa. To our knowledge this is the first community based report from Africa. METHODS: We followed a cohort of 307 (82.1% males) patients with schizophrenia for five years in Butajira, rural Ethiopia. Mortality was recorded using broad rating schedule as well as verbal autopsy. Standardized Mortality Ratio (SMR) was calculated using the mortality in the demographic and surveillance site as a reference. RESULT: Thirty eight (12.4%) patients, 34 men (11.1%) and 4 women (1.3%), died during the five-year follow up period. The mean age (SD) of the deceased for both sexes was 35 (7.35). The difference was not statistically significant (p = 0.69). It was 35.3 (7.4) for men and 32.3 (6.8) for women. The most common cause of death was infection, 18/38 (47.4%) followed by severe malnutrition, 5/38 (13.2%) and suicide 4/38 (10.5%). The overall SMR was 5.98 (95% CI = 4.09 to7.87). Rural residents had lower mortality with adjusted hazard ratio (HR) of 0.30 (95% CI = 0.12-0.69) but insidious onset and antipsychotic treatment for less than 50% of the follow up period were associated with higher mortality, adjusted HR 2.37 (95% CI = 1.04-5. 41) and 2.66(1.054-6.72) respectively. CONCLUSION: The alarmingly high mortality observed in this patient population is of major concern. Most patients died from potentially treatable conditions. Improving medical and psychiatric care as well as provision of basic needs is recommended." [Accessed on December 8, 2011]. http://www.ncbi.nlm.nih.gov/pubmed/21985179.
Journal article: Robert C Green, Lon S Schneider, David A Amato, Andrew P Beelen, Gordon Wilcock, Edward A Swabb, Kenton H Zavitz. Effect of tarenflurbil on cognitive decline and activities of daily living in patients with mild Alzheimer disease: a randomized controlled trial JAMA. 2009;302(23):2557-2564. Abstract: "CONTEXT: Amyloid-beta peptide (Abeta(42)) has been implicated in the pathogenesis of Alzheimer disease (AD). Tarenflurbil, a selective Abeta(42)-lowering agent, demonstrated encouraging results on cognitive and functional outcomes among mildly affected patients in an earlier phase 2 trial. OBJECTIVE: To determine the efficacy, safety, and tolerability of tarenflurbil. DESIGN, SETTING, AND PATIENTS: A multicenter, randomized, double-blind, placebo-controlled trial enrolling patients with mild AD was conducted at 133 trial sites in the United States between February 21, 2005, and April 30, 2008. Concomitant treatment with cholinesterase inhibitors or memantine was permitted. INTERVENTION: Tarenflurbil, 800 mg, or placebo, administered twice a day. MAIN OUTCOME MEASURES: Co-primary efficacy end points were the change from baseline to month 18 in total score on the subscale of the Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog, 80-point version) and Alzheimer Disease Cooperative Studies-activities of daily living (ADCS-ADL) scale. Additional prespecified slope analyses explored the possibility of disease modification. RESULTS: Of the 1684 participants randomized, 1649 were included in the analysis, and 1046 completed the trial. Tarenflurbil had no beneficial effect on the co-primary outcomes (difference in change from baseline to month 18 vs placebo, based on least squares means: 0.1 for ADAS-Cog; 95% CI, -0.9 to 1.1; P = .86 and -0.5 for ADCS-ADL; 95% CI, -1.9 to 0.9; P = .48) using an intent-to-treat analysis. No significant differences occurred in the secondary outcomes. The ADAS-Cog score decreased by 7.1 points over 18 months. The tarenflurbil group had a small increase in frequency of dizziness, anemia, and infections. CONCLUSION: Tarenflurbil did not slow cognitive decline or the loss of activities of daily living in patients with mild AD. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00105547." [Accessed on December 8, 2011]. http://www.ncbi.nlm.nih.gov/pubmed/20009055.
Journal article: Andrew J Cutler, Amir H Kalali, Peter J Weiden, Jennifer Hamilton, Curt D Wolfgang. Four-week, double-blind, placebo- and ziprasidone-controlled trial of iloperidone in patients with acute exacerbations of schizophrenia J Clin Psychopharmacol. 2008;28(2 Suppl 1):S20-28. Abstract: "Iloperidone is a mixed D2/5-HT2 antagonist in development for treatment of schizophrenia. This trial aimed to evaluate the efficacy and safety of a fixed dose of iloperidone in patients with acute exacerbations of schizophrenia. This randomized, placebo-controlled, multicenter study comprised a 1-week titration period and a 3-week double-blind maintenance period. Eligible patients (n = 593) were randomized to iloperidone 24 mg/d, ziprasidone 160 mg/d as an active control, or placebo. Primary efficacy variable was change from baseline in the Positive and Negative Syndrome Scale Total (PANSS-T) score, using a mixed-effects model repeated measures analysis. Iloperidone demonstrated significant reduction versus placebo on the PANSS-T score (P< 0.01). Significant improvement versus placebo was also demonstrated with ziprasidone (P < 0.05). Compared with ziprasidone, iloperidone was associated with lower rates of many adverse events (AEs) that are particularly troublesome with antipsychotics, including sedation, somnolence, extrapyramidal symptoms, akathisia, agitation, and restlessness; iloperidone was associated with higher rates of weight gain, tachycardia, orthostatic hypotension, dizziness, and nasal congestion as reported as an AE. Most AEs were mild to moderate. A similar amount of QT prolongation was observed with both active treatments, although no patient had a treatment-emergent postbaseline corrected QT interval of 500 msec or greater. The incidence of clinically relevant changes in laboratory parameters was comparable between iloperidone and ziprasidone. Iloperidone was associated with a low incidence of extrapyramidal symptoms. Overall, there was improvement in akathisia with iloperidone treatment. Iloperidone treatment was effective, safe, and well tolerated in patients with acute exacerbation of schizophrenia." [Accessed on December 8, 2011]. http://www.ncbi.nlm.nih.gov/pubmed/18334909.
Journal article: Steven G. Potkin, Robert E. Litman, Rosarelis Torres, Curt D. Wolfgang. Efficacy of Iloperidone in the Treatment of Schizophrenia Journal of Clinical Psychopharmacology. 2008;28(Suppl. 1):S4-S11. Abstract: "Iloperidone is an atypical antipsychotic in development for the treatment of schizophrenia. This report examines efficacy results from three 6-week, randomized, double-blind, placebo- and active comparator-controlled studies in patients with schizophrenia or schizoaffective disorder. Multiple doses of iloperidone were studied. Active comparators (haloperidol 15 mg/d, or risperidone 4-8 mg/d) were included to confirm trial validity. The primary protocol-defined efficacy variable in Study 1 was change from baseline to end point in Positive and Negative Syndrome Scale total scores; in Studies 2 and 3, it was change in the Positive and Negative Syndrome Scale-derived Brief Psychiatric Rating Scale scores. Results were assessed through analysis of covariance using last observation carried forward in the intent-to-treat population. In total, 1943 patients were randomized. At least 1 iloperidone dosing group in each study demonstrated significantly better efficacy than placebo (Study 1, iloperidone 12 mg/d [P = 0.047]; Study 2, 4-8 mg/d [P = 0.012] and 10-16 mg/d [P = 0.001]; and Study 3, 20-24 mg/d [P = 0.010]). Active controls were also significantly more effective than placebo in each trial, thus validating the trials. Additional analysis in patients who received active treatment for at least 2 weeks indicated comparable efficacy score reductions at 6 weeks for patients receiving iloperidone 20 to 24 mg/d versus those receiving haloperidol or risperidone. Risk for motor-related adverse events (eg, akathisia and extrapyramidal symptoms) was lower with iloperidone than with risperidone and haloperidol and was generally similar to placebo. These trials indicate that iloperidone is effective for the treatment of schizophrenia." [Accessed on December 8, 2011]. http://journals.lww.com/psychopharmacology/Abstract/2008/04001/Efficacy_of_Iloperidone_in_the_Treatment_of.2.aspx.
Journal article: Susanne Ostrowitzki, Dennis Deptula, Lennart Thurfjell, Frederik Barkhof, Bernd Bohrmann, David J Brooks, William E Klunk, Elizabeth Ashford, Kisook Yoo, et al. Mechanism of Amyloid Removal in Patients With Alzheimer Disease Treated With Gantenerumab Archives of Neurology. 2011. Abstract: "BACKGROUND: Gantenerumab is a fully human anti-Aβ monoclonal antibody in clinical development for the treatment of Alzheimer disease (AD). OBJECTIVES: To investigate whether treatment with gantenerumab leads to a measurable reduction in the level of Aβ amyloid in the brain and to elucidate the mechanism of amyloid reduction. DESIGN: A multicenter, randomized, double-blind, placebo-controlled, ascending-dose positron emission tomographic study. Additionally, ex vivo studies of human brain slices from an independent sample of patients who had AD were performed. SETTING: Three university medical centers. Patients Patients with mild-to-moderate AD. Intervention Two consecutive cohorts of patients received 2 to 7 infusions of intravenous gantenerumab (60 or 200 mg) or placebo every 4 weeks. Brain slices from patients who had AD were coincubated with gantenerumab at increasing concentrations and with human microglial cells. MAIN OUTCOME MEASURES: Percent change in the ratio of regional carbon 11-labeled Pittsburgh Compound B retention in vivo and semiquantitative assessment of gantenerumab-induced phagocytosis ex vivo. RESULTS: Sixteen patients with end-of-treatment positron emission tomographic scans were included in the analysis. The mean (95% CI) percent change from baseline difference relative to placebo (n = 4) in cortical brain amyloid level was -15.6% (95% CI, -42.7 to 11.6) for the 60-mg group (n = 6) and -35.7% (95% CI, -63.5 to -7.9) for the 200-mg group (n = 6). Two patients in the 200-mg group showed transient and focal areas of inflammation or vasogenic edema on magnetic resonance imaging scans at sites with the highest level of amyloid reduction. Gantenerumab induced phagocytosis of human amyloid in a dose-dependent manner ex vivo. CONCLUSION: Gantenerumab treatment resulted in a dose-dependent reduction in brain amyloid level, possibly through an effector cell-mediated mechanism of action." [Accessed on December 8, 2011]. http://www.ncbi.nlm.nih.gov/pubmed/21987394.
This page was written by Steve Simon and is licensed under the Creative Commons Attribution 3.0 United States License. Need more information? I have a page with general help resources. You can also browse for pages similar to this one at Incomplete pages.