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Sample records for 2-year randomized trial

  1. Couple and Individual Adjustment for 2 Years Following a Randomized Clinical Trial Comparing Traditional versus Integrative Behavioral Couple Therapy

    ERIC Educational Resources Information Center

    Christensen, Andrew; Atkins, David C.; Yi, Jean; Baucom, Donald H.; George, William H.

    2006-01-01

    Follow-up data across 2 years were obtained on 130 of 134 couples who were originally part of a randomized clinical trial comparing traditional versus integrative behavioral couple therapy (TBCT vs. IBCT; A. Christensen et al., 2004). Both treatments produced similar levels of clinically significant improvement at 2 years posttreatment (69% of…

  2. A Randomized Controlled Trial of Relationship Education in the U.S. Army: 2-Year Outcomes

    PubMed Central

    Stanley, Scott M.; Rhoades, Galena K.; Loew, Benjamin A.; Allen, Elizabeth S.; Carter, Sarah; Osborne, Laura J.; Prentice, Donnella; Markman, Howard J.

    2014-01-01

    This study examined the effectiveness of an evidence-based, community-delivered adaptation of couple relationship education (CRE; specifically, PREP, The Prevention and Relationship Enhancement Program) delivered at two Army installations. The study is a randomized controlled trial with two years of follow-up, examining marital quality and stability. Sample composition was 662 married couples with a spouse in the U.S. Army. Analyses yielded no evidence of overall enduring intervention effects on relationship quality but couples assigned to intervention at the higher risk site were significantly less likely than controls to be divorced at the two-year follow-up (8.1% vs. 14.9%, p < .01). This effect was moderated by ethnic minority status. Specifically, the impact of the intervention on divorce was strongest for minority couples. The findings add to the literature on who may benefit most from CRE. PMID:25419027

  3. Randomized Controlled Trial of Forward-Planned Intensity Modulated Radiotherapy for Early Breast Cancer: Interim Results at 2 Years

    SciTech Connect

    Barnett, Gillian C.; Wilkinson, Jennifer S.; Moody, Anne M.; Wilson, Charles B.; Twyman, Nicola; Wishart, Gordon C.; Burnet, Neil G.; Coles, Charlotte E.

    2012-02-01

    Purpose: This single-center randomized trial was designed to investigate whether intensity-modulated radiotherapy (IMRT) reduces late toxicity in patients with early-stage breast cancer. Methods and Materials: The standard tangential plans of 1,145 nonselected patients were analyzed. The patients with inhomogeneous plans were randomized to a simple method of forward-planned IMRT or standard radiotherapy (RT). The primary endpoint was serial photographic assessment of breast shrinkage. Results: At 2 years, no significant difference was found in the development of any photographically assessed breast shrinkage between the patients randomized to the interventional or control group (odds ratio, 1.51; 95% confidence interval, 0.83-1.58; p = .41). The patients in the control group were more likely to develop telangiectasia than those in the IMRT group (odds ratio, 1.68; 95% confidence interval 1.13-2.40; p = .009). Poor baseline surgical cosmesis resulted in poor overall cosmesis at 2 years after RT. In patients who had good surgical cosmesis, those randomized to IMRT were less likely to deteriorate to a moderate or poor overall cosmesis than those in the control group (odds ratio, 0.63; 95% confidence interval, 0.39-1.03, p = .061). Conclusions: IMRT can lead to a significant reduction in telangiectasia at comparatively early follow-up of only 2 years after RT completion. An important component of breast induration and shrinkage will actually result from the surgery and not from the RT. Surgical cosmesis is an important determinant of overall cosmesis and could partially mask the longer term benefits of IMRT at this early stage.

  4. Environmental Modifications and 2-Year Measured and Self-reported Stair-Use: A Worksite Randomized Trial

    PubMed Central

    Linde, Jennifer A.; Cousins, Julie M.; Jeffery, Robert W.

    2014-01-01

    Environmental modifications have been shown to increase short-term stair use, longer-term success is unclear. This study assessed the 2-year effectiveness of an environmental intervention promoting worksite stair use. We assessed stair use at work by means of self-reports and infrared beam counters (which send a safe and invisible beam of infrared light from one side of a stairwell to a reflector on the other side; when an individual uses the stairs, the infrared beam is disrupted and an instance of stair use is recorded) at six worksites (three intervention, three control) in a group randomized, controlled worksite weight-gain prevention trial in Minneapolis/St. Paul, MN. Intervention modifications were signs encouraging stair use, music, and art posters in stairwells. We collected data before environmental modifications (2006–2007) and at the end of the 2-year intervention (2008–2009). The intervention had a significant positive effect on stair use measured both objectively and via self-report, with greatest increases reported among those participants who used the stairs least at baseline. Following 2-years of continuously-maintained stairwell modifications, increases in both objectively-measured and self-reported stair use were significantly larger at intervention than control worksites. Study findings suggest that the positive impact of environmental modifications on stair use persist over a longer time period than has been previously demonstrated. Results also indicate that infrequent stair users may be most amenable to the behavior changes encouraged by these environmental enhancements. PMID:23979097

  5. Diabetes Nurse Case Management and Motivational Interviewing for Change (DYNAMIC): Results of a 2-year Randomized Controlled Pragmatic Trial

    PubMed Central

    Gabbay, Robert A.; Añel-Tiangco, Raquel M.; Dellasega, Cheryl; Mauger, David T.; Adelman, Alan; Van Horn, Deborah H.A.

    2013-01-01

    Objective To determine if the addition of nurse case managers (NCMs) trained in motivational interviewing (MI) to usual care would result in improved outcomes in high risk type 2 diabetes patients. Methods A 2-year randomized controlled pragmatic trial randomized 545 patients to usual care control (n=313) or those who received the intervention (n= 232) with additional practice embedded NCM care, including MI-guided behavior change counseling. NCMs received intensive MI training with ongoing fidelity assessment. Results Systolic BP was better in the intervention group (131±15.9 vs. 135±18.2, p < 0.05). HbA1c, LDL, and diastolic BP improved in both groups: HbA1c (control group 9.1% to 8.0%, intervention group 8.8% to 7.8%), LDL (control group 127 to 100 mg/dL, intervention group 128 to 102 mg/dL), diastolic BP (control group 78 to 74 mm Hg, intervention group 80 to 74 mm Hg). Depression symptom scores were better in the intervention group. The reduction in diabetes-related distress approached statistical significance. Conclusions NCMs and MI improved systolic BP and complications screening. The large decrease in HbA1C and LDL in the control group may have obscured any further intervention effect. Although nurses prompted providers for medication titration, strategies to reduce provider clinical inertia might also be needed. Significant findings of the study In patients with type 2 diabetes, an intervention with nurse case management and motivational interviewing improves systolic blood pressure, depression, and screening for complications. What this study adds First study to look at the benefit of the addition of motivational interviewing to nurse case management in the care of the high-risk adult with type 2 diabetes. Particular attention was given to ensuring fidelity to the motivational interviewing approach. PMID:23368423

  6. Effects of Cognitive Enhancement Therapy on Employment Outcomes in Early Schizophrenia: Results from a 2-Year Randomized Trial

    ERIC Educational Resources Information Center

    Eack, Shaun M.; Hogarty, Gerard E.; Greenwald, Deborah P.; Hogarty, Susan S.; Keshavan, Matcheri S.

    2011-01-01

    Objective: To examine the effects of psychosocial cognitive rehabilitation on employment outcomes in a randomized controlled trial for individuals with early course schizophrenia. Method: Early course schizophrenia outpatients (N = 58) were randomly assigned to cognitive enhancement therapy (CET) or an enriched supportive therapy (EST) control and…

  7. Renal Function Following Three Distinct Weight Loss Dietary Strategies During 2 Years of a Randomized Controlled Trial

    PubMed Central

    Tirosh, Amir; Golan, Rachel; Harman-Boehm, Ilana; Henkin, Yaakov; Schwarzfuchs, Dan; Rudich, Assaf; Kovsan, Julia; Fiedler, Georg M.; Blüher, Matthias; Stumvoll, Michael; Thiery, Joachim; Stampfer, Meir J.; Shai, Iris

    2013-01-01

    OBJECTIVE This study addressed the long-term effect of various diets, particularly low-carbohydrate high-protein, on renal function on participants with or without type 2 diabetes. RESEARCH DESIGN AND METHODS In the 2-year Dietary Intervention Randomized Controlled Trial (DIRECT), 318 participants (age, 51 years; 86% men; BMI, 31 kg/m2; mean estimated glomerular filtration rate [eGFR], 70.5 mL/min/1.73 m2; mean urine microalbumin-to-creatinine ratio, 12:12) with serum creatinine <176 μmol/L (eGFR ≥30 mL/min/1.73 m2) were randomized to low-fat, Mediterranean, or low-carbohydrate diets. The 2-year compliance was 85%, and the proportion of protein intake significantly increased to 22% of energy only in the low-carbohydrate diet (P < 0.05 vs. low-fat and Mediterranean). We examined changes in urinary microalbumin and eGFR, estimated by Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration formulas. RESULTS Significant (P < 0.05 within groups) improvements in eGFR were achieved in low-carbohydrate (+5.3% [95% CI 2.1–8.5]), Mediterranean (+5.2% [3.0–7.4]), and low-fat diets (+4.0% [0.9–7.1]) with similar magnitude (P > 0.05) across diet groups. The increased eGFR was at least as prominent in participants with (+6.7%) or without (+4.5%) type 2 diabetes or those with lower baseline renal function of eGFR <60 mL/min/1.73 m2 (+7.1%) versus eGFR ≥60 mL/min/1.73 m2 (+3.7%). In a multivariable model adjusted for age, sex, diet group, type 2 diabetes, use of ACE inhibitors, 2-year weight loss, and change in protein intake (confounders and univariate predictors), only a decrease in fasting insulin (β = −0.211; P = 0.004) and systolic blood pressure (β = −0.25; P < 0.001) were independently associated with increased eGFR. The urine microalbumin-to-creatinine ratio improved similarly across the diets, particularly among participants with baseline sex-adjusted microalbuminuria, with a mean change of −24.8 (P < 0

  8. Group and Individual Treatment of Obsessive-Compulsive Disorder Using Cognitive Therapy and Exposure Plus Response Prevention: A 2-Year Follow-Up of Two Randomized Trials

    ERIC Educational Resources Information Center

    Whittal, Maureen L.; Robichaud, Melisa; Thordarson, Dana S.; McLean, Peter D.

    2008-01-01

    Relatively little is known about the long-term durability of group treatments for obsessive-compulsive disorder (OCD) and contemporary cognitive treatments. The current study investigated the 2-year follow-up results for participants who completed randomized trials of group or individual treatment and received either cognitive therapy (CT) or…

  9. Amoxicillin Plus Metronidazole Therapy for Patients with Periodontitis and Type 2 Diabetes: A 2-year Randomized Controlled Trial.

    PubMed

    Tamashiro, N S; Duarte, P M; Miranda, T S; Maciel, S S; Figueiredo, L C; Faveri, M; Feres, M

    2016-07-01

    The aim of this study was to assess the changes occurring in subgingival biofilm composition and in the periodontal clinical parameters of subjects with periodontitis and type 2 diabetes mellitus (DM) treated by means of scaling and root planing (SRP) only or combined with systemic metronidazole (MTZ) and amoxicillin (AMX). Fifty-eight subjects were randomly assigned to receive SRP only (n = 29) or with MTZ (400 mg/thrice a day [TID]) and AMX (500 mg/TID) (n = 29) for 14 d. Six subgingival plaque samples/subject were analyzed by checkerboard DNA-DNA hybridization for 40 bacterial species at baseline and 3 mo, 1 y, and 2 y posttherapy. At 2 y posttherapy, the antibiotic-treated group harbored lower mean proportions (5.5%) of red complex pathogens than the control group (12.1%) (P < 0.05). The proportions of the Actinomyces species remained stable in the antibiotic group but showed a statistically significant reduction in the control group from 1 to 2 y in subjects achieving a low risk clinical profile for future disease progression (i.e., ≤4 sites with probing depth [PD] ≥5 mm). The test group also had a lower mean number of sites with PD ≥5 mm (3.5 ± 3.4) and a higher percentage of subjects reaching the low risk clinical profile (76%) than the control group (14.7 ± 13.1 and 22%, respectively) (P < 0.05) at 2 y posttreatment. MTZ + AMX intake was the only significant predictor of subjects achieving the low risk at 2 y (odds ratio, 20.9; P = 0.0000). In conclusion, the results of this study showed that the adjunctive use of MTZ + AMX improves the microbiological and clinical outcomes of SRP in the treatment of subjects with generalized chronic periodontitis and type 2 DM up to 2 y (ClinicalTrials.gov NCT02135952). PMID:27013640

  10. Risedronate Prevents Bone Loss in Breast Cancer Survivors: A 2-Year, Randomized, Double-Blind, Placebo-Controlled Clinical Trial

    PubMed Central

    Greenspan, Susan L.; Brufsky, Adam; Lembersky, Barry C.; Bhattacharya, Rajib; Vujevich, Karen T.; Perera, Subashan; Sereika, Susan M.; Vogel, Victor G.

    2014-01-01

    Purpose Limited data are available on the efficacy of oral bisphosphonate therapy in breast cancer survivors. Our goal was to examine prevention of breast cancer–related bone loss in this cohort. Patients and Methods Eighty-seven postmenopausal women after chemotherapy for breast cancer were randomly assigned to once-weekly risedronate 35 mg or placebo for 24 months. Outcomes included bone mineral density (BMD) and turnover markers. Results At study initiation, 13% of patients were on an aromatase inhibitor (AI). After 24 months, there were differences of 1.6 to 2.5% (P < .05) at the spine and hip BMD between the placebo and risedronate groups. At study completion, 44% were on an AI. Adjusting for an AI, women on placebo plus AI had a decrease in BMD of (mean ± SE) 4.8% ± 0.8% at the spine and 2.8% ± 0.5% at the total hip (both P < .001). In women on risedronate + AI, the spine decreased by 2.4% ± 1.1% (P < .05) and was stable at the hip. Women in the placebo group not on an AI, maintained BMD at the spine, and had a 1.2% ± 0.5% loss at the total hip (P < .05). Women who received risedronate but no AI had the greatest improvement in BMD of 2.2% ± 0.9% (P < .05) at the total hip. Bone turnover was reduced with risedronate. There were no differences in adverse events between the groups. Conclusion We conclude that in postmenopausal women with breast cancer with or without AI therapy, once-weekly oral risedronate was beneficial for spine and hip BMD, reduced bone turnover, and was well tolerated. PMID:18427147

  11. Immunogenicity and safety of a 23-valent pneumococcal polysaccharide vaccine in Chinese healthy population aged >2 years: A randomized, double-blinded, active control, phase III trial.

    PubMed

    Kong, Yujia; Zhang, Wei; Jiang, Zhiwei; Wang, Ling; Li, Chanjuan; Li, Yanping; Xia, Jielai

    2015-01-01

    Streptococcus pneumoniae is an important pathogen causing invasive diseases such as sepsis, meningitis, and pneumonia. Vaccines have become the most effective way to prevent pneumococcal infections. This phase III trial was designed to evaluate the immunogenicity and safety of a 23-valent pneumococcal polysaccharide vaccine in Chinese healthy population aged >2 years. We conducted a randomized, double-blinded, active-controlled, multicenter trial in which 1660 healthy population (>2 years of age) were randomly assigned in a 1 : 1 ratio to receive 2 intramuscular doses of either the treatment vaccine or the active control vaccine, PNEUMOVAX 23. The surveillance period was 30 days. The primary end point was the 2-fold increase rate of anti-pneumococcal antibody for all 23 included serotypes in each group. In the intention-to-treat cohort, the 2-fold increase rate of anti-pneumococcal antibody for 23 included serotypes varied from 62.47% to 97.01% in the treatment group, and from 51.49% to 95.77% in the control group. According to -10% non-inferiority margin and 95% confidence intervals of rate difference, almost all included serotypes of the treatment group reached non-inferiority to control group except for serotype 6B, the lower limit of rate difference of which was -10.00%, equal to the non-inferiority margin. The 2-fold increase rates of anti-pneumococcal antibody were significantly higher in the treatment group for serotype 2, 3, 4, 10A, 11A and 20. Furthermore, for all 23 serotypes, IgG geometric mean concentrations (GMCs) at day 30 were significantly higher in treatment group for serotype 2, 3, 4, 9 V, 10A, 11A, 15 B, 18C, 19 A, 22 F and 33 F. Higher geometric mean fold increase (GMFI) were also observed in the treatment group correspondingly. Serious adverse events occurred in 3 of 830 participants in the treatment group (0.36%) and 2 of 830 participants in the control group (0.24%). No death occurred during the trial. The frequencies of both solicited and

  12. A Randomized, Controlled Trial Comparing Autologous Matrix-Induced Chondrogenesis (AMIC®) to Microfracture: Analysis of 1- and 2-Year Follow-Up Data of 2 Centers

    PubMed Central

    Anders, Sven; Volz, Martin; Frick, Hubert; Gellissen, Jörg

    2013-01-01

    Microfracture (MFx) is currently the recommended option for the treatment of small cartilage defects but is not regarded as suitable for the treatment of defects larger than 2.5 cm2. To extent its applicability to medium-sized defects MFx has been combined with a collagen type I/III matrix (Chondro-Gide®). This technique is called Autologous Matrix-Induced Chondrogenesis (AMIC®) and meanwhile a clinically established treatment option for localized full-thickness small- to medium-sized cartilage defects. Despite its more spreading clinical use, clinical data published so far are limited to mainly case report series. In this study, we report the first results of a randomized, controlled trial assessing the efficacy and safety of AMIC® versus MFx. Patients enrolled in 2 centers were included in this analysis. 38 patients (aged 21-50 years, mean defect size 3.4 cm2) were randomized and treated either with MFx, with sutured AMIC® or glued AMIC®. Clinical outcomes (modified Cincinnati and ICRS score) could be assessed in 30 patients at 1-year and 27 patients at 2-years post-operation. Improvements in both scores were seen at 1-and 2-years post-operation, irrespective of the technique used. MRI assessment revealed a satisfactory and homogenous defect filling in the majority of patients. No treatment-related adverse events were reported. This interim analysis confirms the mid-term results for AMIC® reported in literature. It demonstrates clearly that clinical outcomes at 1-year post-operation are maintained at 2-years. Therefore we consider enhancing MFx with Chondro-Gide® is a valid and safe cartilage repair option for small- to medium-sized cartilage defects of the knee. PMID:23730377

  13. Posterolateral instrumented fusion with and without transforaminal lumbar interbody fusion for the treatment of adult isthmic spondylolisthesis: A randomized clinical trial with 2-year follow-up

    PubMed Central

    Etemadifar, Mohammad Reza; Hadi, Abdollah; Masouleh, Mehran Feizi

    2016-01-01

    Background: Spondylolisthesis is a common cause of surgery in patients with lower back pain. Although posterolateral fusion and pedicle screw fixation are a relatively common treatment method for the treatment of spondylolisthesis, controversy exists about the necessity of adding interbody fusion to posterolateral fusion. The aim of our study was to assess the functional disability, pain, and complications in patients with spondylolisthesis treated by posterolateral instrumented fusion (PLF) with and without transforaminal lumbar interbody fusion (TLIF) in a randomized clinical trial. Materials and Methods: From February 2007 to February 2011, 50 adult patients with spondylolisthesis were randomly assigned to be treated with PLF or PLF+TLIF techniques (25 patients in each group) by a single surgeon. Back pain, leg pain, and disability were assessed before treatment and until 2 years after surgical treatment using visual analog scale (VAS) and oswestry disability index (ODI). Patients were also evaluated for postoperative complications such as infection, neurological complications, and instrument failure. Results: All patients completed the 24 months of follow-up. Twenty patients were females and 30 were males. Average age of the patients was 53 ± 11 years for the PLF group and 51 ± 13 for the PLF + TLIF group. Back pain, leg pain, and disability score were significantly improved postoperatively compared to preoperative scores (P < 0.001). At 3 months of follow-up, there was no statistically significant difference in VAS score for back pain and leg pain in both groups; however, after 6 months and 1 year and 2 years follow-up, the reported scores for back pain and leg pain were significantly lower in the PLF+TLIF group (P < 0.05). The ODI score was also significantly lower in the PLF+TLIF group at 1 year and 2 years of follow-up (P < 0.05). One screw breakage and one superficial infection occurred in the PLF+TLIF group, which had no statistical significance (P = 0

  14. Effects of 2-year calorie restriction on circulating levels of IGF-1, IGF-binding proteins and cortisol in nonobese men and women: a randomized clinical trial.

    PubMed

    Fontana, Luigi; Villareal, Dennis T; Das, Sai K; Smith, Steven R; Meydani, Simin N; Pittas, Anastassios G; Klein, Samuel; Bhapkar, Manjushri; Rochon, James; Ravussin, Eric; Holloszy, John O

    2016-02-01

    Young-onset calorie restriction (CR) in rodents decreases serum IGF-1 concentration and increases serum corticosterone levels, which have been hypothesized to play major roles in mediating its anticancer and anti-aging effects. However, little is known on the effects of CR on the IGF-1 system and cortisol in humans. To test the sustained effects of CR on these key hormonal adaptations, we performed a multicenter randomized trial of a 2-year 25% CR intervention in 218 nonobese (body mass index between 22 and 27.8 kg m(-2) ) young and middle-aged (20-50 years age range) men and women. Average CR during the first 6 months was 19.5 ± 0.8% and 9.1 ± 0.7% over the next 18 months of the study. Weight loss averaged 7.6 ± 0.3 kg over the 2-years period of which 71% was fat mass loss (P < 0.0001). Average CR during the CR caused a significant 21% increase in serum IGFBP-1 and a 42% reduction in IGF-1:IGFBP-1 ratio at 2 years (P < 0.008), but did not change IGF-1 and IGF-1:IGFBP-3 ratio levels. Serum cortisol concentrations were slightly but significantly increased by CR at 1 year only (P = 0.003). Calorie restriction had no effect on serum concentrations of PDGF-AB and TGFβ-1. We conclude, on the basis of the present and previous findings, that, in contrast to rodents, humans do not respond to CR with a decrease in serum IGF-1 concentration or with a sustained and biological relevant increase in serum cortisol. However, long-term CR in humans significantly and persistently increases serum IGFBP-1 concentration. PMID:26443692

  15. CAD/CAM ZIRCONIA VS. SLIP-CAST GLASS-INFILTRATED ALUMINA/ZIRCONIA ALL-CERAMIC CROWNS: 2-YEAR RESULTS OF A RANDOMIZED CONTROLLED CLINICAL TRIAL

    PubMed Central

    Çehreli, Murat Cavit; Kökat, Ali Murat; Akça, Kivanç

    2009-01-01

    The aim of this randomized controlled clinical trial was to compare the early clinical outcome of slip-cast glass-infiltrated Alumina/Zirconia and CAD/CAM Zirconia all-ceramic crowns. A total of 30 InCeram® Zirconia and Cercon® Zirconia crowns were fabricated and cemented with a glass ionomer cement in 20 patients. At baseline, 6-month, 1-year, and 2-year recall appointments, Californian Dental Association (CDA) quality evaluation system was used to evaluate the prosthetic replacements, and plaque and gingival index scores were used to explore the periodontal outcome of the treatments. No clinical sign of marginal discoloration, persistent pain and secondary caries was detected in any of the restorations. All InCeram® Zirconia crowns survived during the 2-year period, although one nonvital tooth experienced root fracture coupled with the fracture of the veneering porcelain of the restoration. One Cercon® Zirconia restoration fractured and was replaced. According to the CDA criteria, marginal integrity was rated excellent for InCeram® Zirconia (73%) and Cercon® Zirconia (80%) restorations, respectively. Slight color mismatch rate was higher for InCeram® Zirconia restorations (66%) than Cercon® Zirconia (26%) restorations. Plaque and gingival index scores were mostly zero and almost constant over time. Time-dependent changes in plaque and gingival index scores within and between groups were statistically similar (p>0.05). This clinical study demonstrates that single-tooth InCeram® Zirconia and Cercon® Zirconia crowns have comparable early clinical outcome, both seem as acceptable treatment modalities, and most importantly, all-ceramic alumina crowns strengthened by 25% zirconia can sufficiently withstand functional load in the posterior zone. PMID:19148406

  16. Internet-based treatment of stress urinary incontinence: 1- and 2-year results of a randomized controlled trial with a focus on pelvic floor muscle training

    PubMed Central

    Sjöström, Malin; Umefjord, Göran; Stenlund, Hans; Carlbring, Per; Andersson, Gerhard; Samuelsson, Eva

    2015-01-01

    Objectives To evaluate the long-term effects of two non-face-to-face treatment programmes for stress urinary incontinence (SUI) based on pelvic floor muscle training (PFMT). Subjects and Methods The present study was a randomized controlled trial with online recruitment of 250 community-dwelling women aged 18–70 years with SUI ≥ one time/week. Diagnosis was based on validated self-assessed questionnaires, 2-day bladder diary and telephone interview with a urotherapist. Consecutive computer-generated block randomization was carried out with allocation by an independent administrator to 3 months of treatment with either an internet-based treatment programme (n = 124) or a programme sent by post (n = 126). Both interventions focused mainly on PFMT. The internet group received continuous e-mail support from a urotherapist, whereas the postal group trained on their own. Follow-up was performed after 1 and 2 years via self-assessed postal questionnaires. The primary outcomes were symptom severity (International Consultation on Incontinence Questionnaire Short Form [ICIQ-UI SF]) and condition-specific quality of life (ICIQ-Lower Urinary Tract Symptoms Quality of Life [ICIQ-LUTSqol]). Secondary outcomes were the Patient Global Impression of Improvement, health-specific quality of life (EQ-visual analogue scale [EQ-VAS]), use of incontinence aids, and satisfaction with treatment. There was no face-to-face contact with the participants at any time. Analysis was based on intention-to-treat. Results We lost 32.4% (81/250) of participants to follow-up after 1 year and 38.0% (95/250) after 2 years. With both interventions, we observed highly significant (P < 0.001) improvements with large effect sizes (>0.8) for symptoms and condition-specific quality of life (QoL) after 1 and 2 years, respectively. No significant differences were found between the groups. The mean (sd) changes in symptom score were 3.7 (3.3) for the internet group and 3.2 (3.4) for the postal group (P = 0

  17. Effects of Prednisolone on Disease Progression in Antiretroviral-Untreated HIV Infection: A 2-Year Randomized, Double-Blind Placebo-Controlled Clinical Trial

    PubMed Central

    Kasang, Christa; Kalluvya, Samuel; Majinge, Charles; Kongola, Gilbert; Mlewa, Mathias; Massawe, Irene; Kabyemera, Rogatus; Magambo, Kinanga; Ulmer, Albrecht; Klinker, Hartwig; Gschmack, Eva; Horn, Anne; Koutsilieri, Eleni; Preiser, Wolfgang; Hofmann, Daniela; Hain, Johannes; Müller, Andreas; Dölken, Lars; Weissbrich, Benedikt; Rethwilm, Axel; Stich, August; Scheller, Carsten

    2016-01-01

    Background HIV-disease progression correlates with immune activation. Here we investigated whether corticosteroid treatment can attenuate HIV disease progression in antiretroviral-untreated patients. Methods Double-blind, placebo-controlled randomized clinical trial including 326 HIV-patients in a resource-limited setting in Tanzania (clinicaltrials.gov NCT01299948). Inclusion criteria were a CD4 count above 300 cells/μl, the absence of AIDS-defining symptoms and an ART-naïve therapy status. Study participants received 5 mg prednisolone per day or placebo for 2 years. Primary endpoint was time to progression to an AIDS-defining condition or to a CD4-count below 200 cells/μl. Results No significant change in progression towards the primary endpoint was observed in the intent-to-treat (ITT) analysis (19 cases with prednisolone versus 28 cases with placebo, p = 0.1407). In a per-protocol (PP)-analysis, 13 versus 24 study participants progressed to the primary study endpoint (p = 0.0741). Secondary endpoints: Prednisolone-treatment decreased immune activation (sCD14, suPAR, CD38/HLA-DR/CD8+) and increased CD4-counts (+77.42 ± 5.70 cells/μl compared to -37.42 ± 10.77 cells/μl under placebo, p < 0.0001). Treatment with prednisolone was associated with a 3.2-fold increase in HIV viral load (p < 0.0001). In a post-hoc analysis stratifying for sex, females treated with prednisolone progressed significantly slower to the primary study endpoint than females treated with placebo (ITT-analysis: 11 versus 21 cases, p = 0.0567; PP-analysis: 5 versus 18 cases, p = 0.0051): No changes in disease progression were observed in men. Conclusions This study could not detect any significant effects of prednisolone on disease progression in antiretroviral-untreated HIV infection within the intent-to-treat population. However, significant effects were observed on CD4 counts, immune activation and HIV viral load. This study contributes to a better understanding of the role of immune

  18. Evaluation of Lumbar Facet Joint Nerve Blocks in Managing Chronic Low Back Pain: A Randomized, Double-Blind, Controlled Trial with a 2-Year Follow-Up

    PubMed Central

    Manchikanti, Laxmaiah; Singh, Vijay; Falco, Frank J.E.; Cash, Kimberly A.; Pampati, Vidyasagar

    2010-01-01

    Study Design: A randomized, double-blind, controlled trial. Objective: To determine the clinical effectiveness of therapeutic lumbar facet joint nerve blocks with or without steroids in managing chronic low back pain of facet joint origin. Summary of Background Data: Lumbar facet joints have been shown as the source of chronic pain in 21% to 41% of low back patients with an average prevalence of 31% utilizing controlled comparative local anesthetic blocks. Intraarticular injections, medial branch blocks, and radiofrequency neurotomy of lumbar facet joint nerves have been described in the alleviation of chronic low back pain of facet joint origin. Methods: The study included 120 patients with 60 patients in each group with local anesthetic alone or local anesthetic and steroids. The inclusion criteria was based upon a positive response to diagnostic controlled, comparative local anesthetic lumbar facet joint blocks. Outcome measures included the numeric rating scale (NRS), Oswestry Disability Index (ODI), opioid intake, and work status, at baseline, 3, 6, 12, 18, and 24 months. Results: Significant improvement with significant pain relief of ≥ 50% and functional improvement of ≥ 40% were observed in 85% in Group 1, and 90% in Group II, at 2-year follow-up. The patients in the study experienced significant pain relief for 82 to 84 weeks of 104 weeks, requiring approximately 5 to 6 treatments with an average relief of 19 weeks per episode of treatment. Conclusions: Therapeutic lumbar facet joint nerve blocks, with or without steroids, may provide a management option for chronic function-limiting low back pain of facet joint origin. PMID:20567613

  19. Cost effectiveness of disc prosthesis versus lumbar fusion in patients with chronic low back pain: randomized controlled trial with 2-year follow-up.

    PubMed

    Fritzell, Peter; Berg, Svante; Borgström, Fredrik; Tullberg, Tycho; Tropp, Hans

    2011-07-01

    This randomized controlled health economic study assesses the cost-effectiveness of the concept of total disc replacement (TDR) (Charité/Prodisc/Maverick) when compared with the concept of instrumented lumbar fusion (FUS) [posterior lumbar fusion (PLF) /posterior lumbar interbody fusion (PLIF)]. Social and healthcare perspectives after 2 years are reported. In all, 152 patients were randomized to either TDR (n = 80) or lumbar FUS (n = 72). Cost to society (total mean cost/patient, Swedish kronor = SEK, standard deviation) for TDR was SEK 599,560 (400,272), and for lumbar FUS SEK 685,919 (422,903) (ns). The difference was not significant: SEK 86,359 (-45,605 to 214,332). TDR was significantly less costly from a healthcare perspective, SEK 22,996 (1,202 to 43,055). Number of days on sick leave among those who returned to work was 185 (146) in the TDR group, and 252 (189) in the FUS group (ns). Using EQ-5D, the total gain in quality adjusted life years (QALYs) over 2 years was 0.41 units for TDR and 0.40 units for FUS (ns). Based on EQ-5D, the incremental cost-effectiveness ratio (ICER) of using TDR instead of FUS was difficult to analyze due to the "non-difference" in treatment outcome, which is why cost/QALY was not meaningful to define. Using cost-effectiveness probabilistic analysis, the net benefit (with CI) was found to be SEK 91,359 (-73,643 to 249,114) (ns). We used the currency of 2006 where 1 EURO = 9.26 SEK and 1 USD = 7.38 SEK. It was not possible to state whether TDR or FUS is more cost-effective after 2 years. Since disc replacement and lumbar fusion are based on different conceptual approaches, it is important to follow these results over time. PMID:21053028

  20. Assessment of effectiveness of percutaneous adhesiolysis and caudal epidural injections in managing post lumbar surgery syndrome: 2-year follow-up of a randomized, controlled trial

    PubMed Central

    Manchikanti, Laxmaiah; Singh, Vijay; Cash, Kimberly A; Pampati, Vidyasagar

    2012-01-01

    Background The literature is replete with evaluations of failed surgery, illustrating a 9.5%–25% reoperation rate. Speculated causes of post lumbar surgery syndrome include epidural fibrosis, acquired stenosis, recurrent disc herniation, sacroiliac joint pain, and facet joint pain among other causes. Methods Patients (n = 120) were randomly assigned to two groups with a 2-year follow-up. Group I (control group, n = 60) received caudal epidural injections with catheterization up to S3 with local anesthetic (lidocaine 2%, 5 mL), nonparticulate betamethasone (6 mg, 1 mL), and 6 mL of 0.9% sodium chloride solution. Group II (intervention group, n = 60) received percutaneous adhesiolysis of the targeted area, with targeted delivery of lidocaine 2% (5 mL), 10% hypertonic sodium chloride solution (6 mL), and nonparticulate betamethasone (6 mg). The multiple outcome measures included the Numeric Rating Scale, the Oswestry Disability Index 2.0, employment status, and opioid intake with assessments at 3, 6, 12, 18, and 24 months posttreatment. Primary outcome was defined as 50% improvement in pain and Oswestry Disability Index scores. Results Significant improvement with at least 50% relief with pain and improvement in functional status was illustrated in 82% of patients at the 2-year follow-up in the intervention group compared to 5% in the control group receiving caudal epidural injections. The average number of procedures over a period of 2 years in Group II was 6.4 ± 2.35 with overall total relief of approximately 78 weeks out of 104 weeks. Conclusion The results of this study show significant improvement in 82% of patients over a period of 2 years with an average of six to seven procedures of 1-day percutaneous adhesiolysis in patients with failed back surgery syndrome. PMID:23293536

  1. Dasatinib or imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: 2-year follow-up from a randomized phase 3 trial (DASISION).

    PubMed

    Kantarjian, Hagop M; Shah, Neil P; Cortes, Jorge E; Baccarani, Michele; Agarwal, Mohan B; Undurraga, María Soledad; Wang, Jianxiang; Ipiña, Juan Julio Kassack; Kim, Dong-Wook; Ogura, Michinori; Pavlovsky, Carolina; Junghanss, Christian; Milone, Jorge H; Nicolini, Franck E; Robak, Tadeusz; Van Droogenbroeck, Jan; Vellenga, Edo; Bradley-Garelik, M Brigid; Zhu, Chao; Hochhaus, Andreas

    2012-02-01

    Dasatinib is a highly potent BCR-ABL inhibitor with established efficacy and safety in imatinib-resistant/-intolerant patients with chronic myeloid leukemia (CML). In the phase 3 DASISION trial, patients with newly diagnosed chronic-phase (CP) CML were randomized to receive dasatinib 100 mg (n = 259) or imatinib 400 mg (n = 260) once daily. Primary data showed superior efficacy for dasatinib compared with imatinib after 12 months, including significantly higher rates of complete cytogenetic response (CCyR), confirmed CCyR (primary end point), and major molecular response (MMR). Here, 24-month data are presented. Cumulative response rates by 24 months in dasatinib and imatinib arms were: CCyR in 86% versus 82%, MMR in 64% versus 46%, and BCR-ABL reduction to ≤ 0.0032% (4.5-log reduction) in 17% versus 8%. Transformation to accelerated-/ blast-phase CML on study occurred in 2.3% with dasatinib versus 5.0% with imatinib. BCR-ABL mutations, assessed after discontinuation, were detected in 10 patients in each arm. In safety analyses, fluid retention, superficial edema, myalgia, vomiting, and rash were less frequent with dasatinib compared with imatinib, whereas pleural effusion and grade 3/4 thrombocytopenia were more frequent with dasatinib. Overall, dasatinib continues to show faster and deeper responses compared with imatinib, supporting first-line use of dasatinib in patients with newly diagnosed CML-CP. This study was registered at ClinicalTrials.gov: NCT00481247. PMID:22160483

  2. Dasatinib or imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: 2-year follow-up from a randomized phase 3 trial (DASISION)

    PubMed Central

    Shah, Neil P.; Cortes, Jorge E.; Baccarani, Michele; Agarwal, Mohan B.; Undurraga, María Soledad; Wang, Jianxiang; Kassack Ipiña, Juan Julio; Kim, Dong-Wook; Ogura, Michinori; Pavlovsky, Carolina; Junghanss, Christian; Milone, Jorge H.; Nicolini, Franck E.; Robak, Tadeusz; Van Droogenbroeck, Jan; Vellenga, Edo; Bradley-Garelik, M. Brigid; Zhu, Chao; Hochhaus, Andreas

    2012-01-01

    Dasatinib is a highly potent BCR-ABL inhibitor with established efficacy and safety in imatinib-resistant/-intolerant patients with chronic myeloid leukemia (CML). In the phase 3 DASISION trial, patients with newly diagnosed chronic-phase (CP) CML were randomized to receive dasatinib 100 mg (n = 259) or imatinib 400 mg (n = 260) once daily. Primary data showed superior efficacy for dasatinib compared with imatinib after 12 months, including significantly higher rates of complete cytogenetic response (CCyR), confirmed CCyR (primary end point), and major molecular response (MMR). Here, 24-month data are presented. Cumulative response rates by 24 months in dasatinib and imatinib arms were: CCyR in 86% versus 82%, MMR in 64% versus 46%, and BCR-ABL reduction to ≤ 0.0032% (4.5-log reduction) in 17% versus 8%. Transformation to accelerated-/ blast-phase CML on study occurred in 2.3% with dasatinib versus 5.0% with imatinib. BCR-ABL mutations, assessed after discontinuation, were detected in 10 patients in each arm. In safety analyses, fluid retention, superficial edema, myalgia, vomiting, and rash were less frequent with dasatinib compared with imatinib, whereas pleural effusion and grade 3/4 thrombocytopenia were more frequent with dasatinib. Overall, dasatinib continues to show faster and deeper responses compared with imatinib, supporting first-line use of dasatinib in patients with newly diagnosed CML-CP. This study was registered at ClinicalTrials.gov: NCT00481247. PMID:22160483

  3. Results of a 2-year randomized, controlled obesity prevention trial: Effects on diet, activity and sleep behaviors in an at-risk young adult population.

    PubMed

    Laska, Melissa N; Lytle, Leslie A; Nanney, Marilyn S; Moe, Stacey G; Linde, Jennifer A; Hannan, Peter J

    2016-08-01

    Excess weight gain tends to occur in young adulthood. However, research examining effective weight-related interventions for this age group has been limited. As one of seven trials in the EARLY Trials consortium (Early Adult Reduction of weight through LifestYle intervention), the CHOICES Study (Choosing Healthy Options in College Environments and Settings) tested effects of a technology-integrated, young adult weight gain prevention intervention. It was a randomized controlled trial with assessments at baseline (2011) and 4-, 12- and 24-months post-intervention initiation and included 441 participants (ages 18-35) who were students at three Minnesota community colleges. The 24-month intervention included a 1-credit academic course and social networking and support online intervention. This analysis examined effects on 12 secondary behavioral outcomes across three domains: diet (fast food, sugary beverages, breakfast, at-home meal preparation), physical activity/screen time (minutes and energy expenditure in leisure time physical activity, television viewing, leisure time computer use) and sleep (hours of sleep, time required to fall asleep, days not getting enough rest, difficulty staying awake). The intervention resulted in significant reductions in fast food (p=0.007) but increases in difficulty staying awake (p=0.015). There was limited evidence of other behavior changes at 4months (0.05

  4. Treatment Differences in the Therapeutic Relationship and Introject during a 2-Year Randomized Controlled Trial of Dialectical Behavior Therapy versus Nonbehavioral Psychotherapy Experts for Borderline Personality Disorder

    ERIC Educational Resources Information Center

    Bedics, Jamie D.; Atkins, David C.; Comtois, Katherine A.; Linehan, Marsha M.

    2012-01-01

    Objective: The present study explored the role of the therapeutic relationship and introject during the course of dialectical behavior therapy (DBT; Linehan, 1993) for the treatment of borderline personality disorder. Method: Women meeting "DSM-IV" criteria for borderline personality disorder (N = 101) were randomized to receive DBT or community…

  5. Polyadenylic-polyuridylic acid as an adjuvant in resectable colorectal carcinoma: a 6 1/2 year follow-up analysis of a multicentric double blind randomized trial.

    PubMed

    Lacour, J; Laplanche, A; Malafosse, M; Gallot, D; Julien, M; Rotman, N; Guivarc'h, M; Roullet-Audy, J C; Lasser, P; Hautefeuille, P

    1992-12-01

    In a double blind study, patients with operable carcinoma of the colon and the upper rectum, who have undergone a macroscopically complete resection of their tumor, were randomized to receive either (i) polyadenylic-polyuridylic acid (AU), one i.v. injection of 60 mg (in 50 ml of solution) once a week for 6 weeks, or (ii) a placebo (P) one i.v. injection of 50 ml of a saline solution with the same schedule. From January 1983 to December 1986, 288 patients were enrolled: 145 in AU group and 143 in P group. The main clinical and pathological characteristics were equally distributed throughout the two groups. There was a significant difference (P < 0.02) in the overall survival (OS) between the two groups, in favor of the P group. The 5-year OS rate was 68% (SD = 4%) in the AU group versus 81% (SD = 3%) in the P group. Thus, AU as a single adjuvant, appears to be ineffective and therefore has no indication in the treatment of colorectal carcinoma. PMID:1478293

  6. The Role of Thoracic Medial Branch Blocks in Managing Chronic Mid and Upper Back Pain: A Randomized, Double-Blind, Active-Control Trial with a 2-Year Followup

    PubMed Central

    Manchikanti, Laxmaiah; Singh, Vijay; Falco, Frank J. E.; Cash, Kimberly A.; Pampati, Vidyasagar; Fellows, Bert

    2012-01-01

    Study Design. A randomized, double-blind, active-control trial. Objective. To determine the clinical effectiveness of therapeutic thoracic facet joint nerve blocks with or without steroids in managing chronic mid back and upper back pain. Summary of Background Data. The prevalence of thoracic facet joint pain has been established as 34% to 42%. Multiple therapeutic techniques utilized in managing chronic thoracic pain of facet joint origin include medial branch blocks, radiofrequency neurotomy, and intraarticular injections. Methods. This randomized double-blind active controlled trial was performed in 100 patients with 50 patients in each group who received medial branch blocks with local anesthetic alone or local anesthetic and steroids. Outcome measures included the numeric rating scale (NRS), Oswestry Disability Index (ODI), opioid intake, and work status, at baseline, 3, 6, 12, 18, and 24 months. Results. Significant improvement with significant pain relief and functional status improvement of 50% or more were observed in 80% of the patients in Group I and 84% of the patients in Group II at 2-year followup. Conclusions. Therapeutic medial branch blocks of thoracic facets with or without steroids may provide a management option for chronic function-limiting thoracic pain of facet joint origin. PMID:22851967

  7. Influence of intravenous amifostine on xerostomia, tumor control, and survival after radiotherapy for head-and- neck cancer: 2-year follow-up of a prospective, randomized, phase III trial

    SciTech Connect

    Wasserman, Todd H. . E-mail: twasserman@bellsouth.net; Brizel, David M.; Henke, Michael; Monnier, Alain; Eschwege, Francois; Sauer, Rolf; Strnad, Vratislav

    2005-11-15

    Purpose: To evaluate chronic xerostomia and tumor control 18 and 24 months after initial treatment with amifostine in a randomized controlled trial of patients with head-and-neck cancer; at 12 months after radiotherapy (RT), amifostine had been shown to reduce xerostomia without changing tumor control. Methods and Materials: Adults with head-and-neck cancer who underwent once-daily RT for 5-7 weeks (total dose, 50-70 Gy) received either open-label amifostine (200 mg/m{sup 2} i.v.) 15-30 min before each fraction of radiation (n = 150) or RT alone (control; n = 153). Results: Amifostine administration was associated with a reduced incidence of Grade {>=}2 xerostomia over 2 years of follow-up (p = 0.002), an increase in the proportion of patients with meaningful (>0.1 g) unstimulated saliva production at 24 months (p = 0.011), and reduced mouth dryness scores on a patient benefit questionnaire at 24 months (p < 0.001). Locoregional control rate, progression-free survival, and overall survival were not significantly different between the amifostine group and the control group. Conclusions: Amifostine administration during head-and-neck RT reduces the severity and duration of xerostomia 2 years after treatment and does not seem to compromise locoregional control rates, progression-free survival, or overall survival.

  8. A Randomized Controlled Trial to Examine the Effect of 2-Year Vitamin B12 and Folic Acid Supplementation on Physical Performance, Strength, and Falling: Additional Findings from the B-PROOF Study.

    PubMed

    Swart, Karin M A; Ham, Annelies C; van Wijngaarden, Janneke P; Enneman, Anke W; van Dijk, Suzanne C; Sohl, Evelien; Brouwer-Brolsma, Elske M; van der Zwaluw, Nikita L; Zillikens, M Carola; Dhonukshe-Rutten, Rosalie A M; van der Velde, Nathalie; Brug, Johannes; Uitterlinden, André G; de Groot, Lisette C P G M; Lips, Paul; van Schoor, Natasja M

    2016-01-01

    Elevated homocysteine concentrations are associated with a decline in physical function in elderly persons. Homocysteine-lowering therapy may slow down this decline. This study aimed to examine the effect of a 2-year intervention of vitamin B12 and folic acid supplementation on physical performance, handgrip strength, and risk of falling in elderly subjects in a double-blind, randomized placebo-controlled trial. Participants aged ≥65 years with elevated plasma homocysteine concentrations [12-50 µmol/L (n = 2919)] were randomly assigned to daily supplementation of 500 µg vitamin B12, 400 µg folic acid, and 600 IU vitamin D3, or to placebo with 600 IU vitamin D3. Physical performance (range 0-12) and handgrip strength (kg) were measured at baseline and after 2 years. Falls were reported prospectively on a research calendar. Intention-to-treat (primary) and per-protocol (secondary) analyses were performed. Physical performance level and handgrip strength significantly decreased during the follow-up period, but this decline did not differ between groups. Moreover, time to first fall was not significantly different (HR: 1.0, 95% CI 0.9-1.2). Secondary analyses on a per-protocol base identified an interaction effect with age on physical performance. In addition, the treatment was associated with higher follow-up scores on the walking test (cumulative OR: 1.3, 95% CI 1.1-1.5). Two-year supplementation of vitamin B12 and folic acid was neither effective in reducing the age-related decline in physical performance and handgrip strength, nor in the prevention of falling in elderly persons. Despite the overall null-effect, the results provide indications for a positive effect of the intervention on gait, as well as on physical performance among compliant persons >80 years. These effects should be further tested in future studies. PMID:26412463

  9. Cost-utility analysis modeling at 2-year follow-up for cervical disc arthroplasty versus anterior cervical discectomy and fusion: A single-center contribution to the randomized controlled trial

    PubMed Central

    Warren, Daniel; Andres, Tate; Hoelscher, Christian; Ricart-Hoffiz, Pedro; Bendo, John; Goldstein, Jeffrey

    2013-01-01

    Background Patients with cervical disc herniations resulting in radiculopathy or myelopathy from single level disease have traditionally been treated with Anterior Cervical Discectomy and Fusion (ACDF), yet Cervical Disc Arthroplasty (CDA) is a new alternative. Expert suggestion of reduced adjacent segment degeneration is a promising future result of CDA. A cost-utility analysis of these procedures with long-term follow-up has not been previously reported. Methods We reviewed single institution prospective data from a randomized trial comparing single-level ACDF and CDA in cervical disc disease. Both Medicare reimbursement schedules and actual hospital cost data for peri-operative care were separately reviewed and analyzed to estimate the cost of treatment of each patient. QALYs were calculated at 1 and 2 years based on NDI and SF-36 outcome scores, and incremental cost effectiveness ratio (ICER) analysis was performed to determine relative cost-effectiveness. Results Patients of both groups showed improvement in NDI and SF-36 outcome scores. Medicare reimbursement rates to the hospital were $11,747 and $10,015 for ACDF and CDA, respectively; these figures rose to $16,162 and $13,171 when including physician and anesthesiologist reimbursement. The estimated actual cost to the hospital of ACDF averaged $16,108, while CDA averaged $16,004 (p = 0.97); when including estimated physicians fees, total hospital costs came to $19,811 and $18,440, respectively. The cost/QALY analyses therefore varied widely with these discrepancies in cost values. The ICERs of ACDF vs CDA with Medicare reimbursements were $18,593 (NDI) and $19,940 (SF-36), while ICERs based on actual total hospital cost were $13,710 (NDI) and $9,140 (SF-36). Conclusions We confirm the efficacy of ACDF and CDA in the treatment of cervical disc disease, as our results suggest similar clinical outcomes at one and two year follow-up. The ICER suggests that the non-significant added benefit via ACDF comes at a

  10. Cluster Randomized Controlled Trial

    PubMed Central

    Young, John; Chapman, Katie; Nixon, Jane; Patel, Anita; Holloway, Ivana; Mellish, Kirste; Anwar, Shamaila; Breen, Rachel; Knapp, Martin; Murray, Jenni; Farrin, Amanda

    2015-01-01

    Background and Purpose— We developed a new postdischarge system of care comprising a structured assessment covering longer-term problems experienced by patients with stroke and their carers, linked to evidence-based treatment algorithms and reference guides (the longer-term stroke care system of care) to address the poor longer-term recovery experienced by many patients with stroke. Methods— A pragmatic, multicentre, cluster randomized controlled trial of this system of care. Eligible patients referred to community-based Stroke Care Coordinators were randomized to receive the new system of care or usual practice. The primary outcome was improved patient psychological well-being (General Health Questionnaire-12) at 6 months; secondary outcomes included functional outcomes for patients, carer outcomes, and cost-effectiveness. Follow-up was through self-completed postal questionnaires at 6 and 12 months. Results— Thirty-two stroke services were randomized (29 participated); 800 patients (399 control; 401 intervention) and 208 carers (100 control; 108 intervention) were recruited. In intention to treat analysis, the adjusted difference in patient General Health Questionnaire-12 mean scores at 6 months was −0.6 points (95% confidence interval, −1.8 to 0.7; P=0.394) indicating no evidence of statistically significant difference between the groups. Costs of Stroke Care Coordinator inputs, total health and social care costs, and quality-adjusted life year gains at 6 months, 12 months, and over the year were similar between the groups. Conclusions— This robust trial demonstrated no benefit in clinical or cost-effectiveness outcomes associated with the new system of care compared with usual Stroke Care Coordinator practice. Clinical Trial Registration— URL: http://www.controlled-trials.com. Unique identifier: ISRCTN 67932305. PMID:26152298

  11. Comparative Efficacy and Durability of Continuation Phase Cognitive Therapy for Preventing Recurrent Depression: Design of a Double-Blinded, Fluoxetine- and Pill-Placebo–Controlled, Randomized Trial with 2-Year Follow-up

    PubMed Central

    Thase, Michael E.

    2010-01-01

    Background Major depressive disorder (MDD) is highly prevalent and associated with disability and chronicity. Although cognitive therapy (CT) is an effective short-term treatment for MDD, a significant proportion of responders subsequently suffer relapses or recurrences. Purpose This design prospectively evaluates: 1) a method to discriminate CT-treated responders at lower versus higher risk for relapse; and 2) the subsequent durability of 8-month continuation phase therapies in randomized higher risk responders followed for an additional 24-months. The primary prediction is: after protocol treatments are stopped, higher risk patients randomly assigned to continuation phase CT (C-CT) will have a lower risk of relapse/recurrence than those randomized to fluoxetine (FLX). Methods Outpatients, aged 18 to 70 years, with recurrent MDD received 12–14 weeks of CT provided by 15 experienced therapists from two sites. Responders (i.e., no MDD and 17-item Hamilton Rating Scale for Depression ≤ 12) were stratified into higher and lower risk groups based on stability of remission during the last 6 weeks of CT. The lower risk group entered follow-up for 32 months; the higher risk group was randomized to 8 months of continuation phase therapy with either C-CT or clinical management plus either double-blinded FLX or pill placebo. Following the continuation phase, higher risk patients were followed by blinded evaluators for 24 months. Results The trial began in 2000. Enrollment is complete (N=523). The follow-up continues. Conclusions The trial evaluates the preventive effects and durability of acute and continuation phase treatments in the largest known sample of CT responders collected worldwide. PMID:20451668

  12. Efficacy and safety of finasteride therapy for benign prostatic hyperplasia: results of a 2-year randomized controlled trial (the PROSPECT study). PROscar Safety Plus Efficacy Canadian Two year Study.

    PubMed Central

    Nickel, J C; Fradet, Y; Boake, R C; Pommerville, P J; Perreault, J P; Afridi, S K; Elhilali, M M

    1996-01-01

    OBJECTIVE: To evaluate the efficacy and safety of 2 years' treatment of moderate benign prostatic hyperplasia (BPH) with finasteride. DESIGN: Double-blind, parallel-group, placebo-controlled, multicentre, prospective randomized study. SETTING: Outpatient care in 28 centres across Canada. PARTICIPANTS: Men aged 45 to 80, in good health, with moderate BPH and no evidence of prostate cancer. A total of 613 men were entered into the study; 472 completed the 2 years of treatment. INTERVENTION: After 1 month of receiving a placebo (run-in period), patients were given either finasteride (5 mg/d) or a placebo for 2 years. OUTCOME MEASURES: Efficacy: changes from baseline in BPH symptom scores, maximum urinary flow rates and prostate volume. Safety: onset, course and resolution of all adverse events during the treatment period. RESULTS: In the efficacy analyses the mean BPH symptom scores decreased 2.1 points (from 15.8 to 13.7) in the finasteride group, as compared with a decrease of 0.7 points (from 16.6 to 15.9) in the placebo group (P < or = 0.01). The maximum urinary flow rate increased by a mean of 1.4 mL/s (from 11.1 to 12.5 mL/s) in the finasteride group, as compared with an increase of 0.3 mL/s (from 10.9 to 11.2 mL/s) in the placebo group (p < or = 0.01). The mean prostate volume decreased by 21% (from a mean volume of 44.1 cm3 at baseline) in the treatment group; it increased by 8.4% (from a mean volume of 45.8 cm3 at baseline) in the placebo group (p < or = 0.01). In the safety analysis, the proportion of patients who experienced any adverse event was similar in the two groups (81.0% in the treatment group and 81.2% in the placebo group). However, the incidence of adverse events related to sexual dysfunction were significantly higher in the finasteride group than in the placebo group (ejaculation disorder 7.7% v. 1.7% and impotence 15.8% v. 6.3%; p < or = 0.01 for both parameters). CONCLUSION: Finasteride is a well-tolerated and effective alternative to watchful

  13. Treatment differences in the therapeutic relationship and introject during a 2-year randomized controlled trial of dialectical behavior therapy versus non-behavioral psychotherapy experts for borderline personality disorder

    PubMed Central

    Bedics, Jamie D.; Atkins, David C.; Comtois, Katherine A.; Linehan, Marsha M.

    2011-01-01

    Objective The purpose of the present study was to explore the role of the therapeutic relationship and introject during the course of dialectical behavior therapy (DBT; Linehan, 1993) for the treatment of borderline personality disorder. Method Women meeting DSM-IV criteria for borderline personality disorder (N = 101) were randomized to receive DBT or community treatment by experts. The Structural Analysis of Social Behavior (SASB; Benjamin, 1974) was used to measure both the therapeutic relationship and introject. Results Using hierarchical linear modeling, DBT patients reported the development of a more positive introject including significantly greater self-affirmation, self-love, self-protection, and less self-attack during the course of treatment and one-year follow-up relative to community treatment by experts. The therapeutic relationship did not have an independent effect on intrapsychic or symptomatic outcome but did interact with treatment. DBT patients who perceived their therapist as affirming and protecting reported less frequent occurrences of non-suicidal self-injury. Conclusions The study showed positive intrapsychic change during DBT while emphasizing the importance of affirmation and control in the therapeutic relationship. Results are discussed in the context of understanding the mechanisms of change in DBT. PMID:22061867

  14. The Design of Cluster Randomized Crossover Trials

    ERIC Educational Resources Information Center

    Rietbergen, Charlotte; Moerbeek, Mirjam

    2011-01-01

    The inefficiency induced by between-cluster variation in cluster randomized (CR) trials can be reduced by implementing a crossover (CO) design. In a simple CO trial, each subject receives each treatment in random order. A powerful characteristic of this design is that each subject serves as its own control. In a CR CO trial, clusters of subjects…

  15. Efficacy Trial of a Brief Cognitive-Behavioral Depression Prevention Program for High-Risk Adolescents: Effects at 1- and 2-Year Follow-Up

    ERIC Educational Resources Information Center

    Stice, Eric; Rohde, Paul; Gau, Jeff M.; Wade, Emily

    2010-01-01

    Objective: To evaluate the effects of a brief group cognitive-behavioral (CB) depression prevention program for high-risk adolescents with elevated depressive symptoms at 1- and 2-year follow-up. Method: In this indicated prevention trial, 341 at-risk youths were randomized to a group CB intervention, group supportive expressive intervention, CB…

  16. The HEART Pathway Randomized Trial

    PubMed Central

    Mahler, Simon A.; Riley, Robert F.; Hiestand, Brian C.; Russell, Gregory B.; Hoekstra, James W.; Lefebvre, Cedric W.; Nicks, Bret A.; Cline, David M.; Askew, Kim L.; Elliott, Stephanie B.; Herrington, David M.; Burke, Gregory L.; Miller, Chadwick D.

    2015-01-01

    Background The HEART Pathway is a decision aid designed to identify emergency department patients with acute chest pain for early discharge. No randomized trials have compared the HEART Pathway with usual care. Methods and Results Adult emergency department patients with symptoms related to acute coronary syndrome without ST-elevation on ECG (n=282) were randomized to the HEART Pathway or usual care. In the HEART Pathway arm, emergency department providers used the HEART score, a validated decision aid, and troponin measures at 0 and 3 hours to identify patients for early discharge. Usual care was based on American College of Cardiology/American Heart Association guidelines. The primary outcome, objective cardiac testing (stress testing or angiography), and secondary outcomes, index length of stay, early discharge, and major adverse cardiac events (death, myocardial infarction, or coronary revascularization), were assessed at 30 days by phone interview and record review. Participants had a mean age of 53 years, 16% had previous myocardial infarction, and 6% (95% confidence interval, 3.6%–9.5%) had major adverse cardiac events within 30 days of randomization. Compared with usual care, use of the HEART Pathway decreased objective cardiac testing at 30 days by 12.1% (68.8% versus 56.7%; P=0.048) and length of stay by 12 hours (9.9 versus 21.9 hours; P=0.013) and increased early discharges by 21.3% (39.7% versus 18.4%; P<0.001). No patients identified for early discharge had major adverse cardiac events within 30 days. Conclusions The HEART Pathway reduces objective cardiac testing during 30 days, shortens length of stay, and increases early discharges. These important efficiency gains occurred without any patients identified for early discharge suffering MACE at 30 days. PMID:25737484

  17. Randomization in clinical trials: conclusions and recommendations.

    PubMed

    Lachin, J M; Matts, J P; Wei, L J

    1988-12-01

    The statistical properties of simple (complete) randomization, permuted-block (or simply blocked) randomization, and the urn adaptive biased-coin randomization are summarized. These procedures are contrasted to covariate adaptive procedures such as minimization and to response adaptive procedures such as the play-the-winner rule. General recommendations are offered regarding the use of complete, permuted-block, or urn randomization. In a large double-masked trial, any of these procedures may be acceptable. For a given trial, the relative merits of each procedure should be carefully weighed in relation to the characteristics of the trial. Important considerations are the size of the trial, overall as well as within the smallest subgroup to be employed in a subgroup-specific analysis, whether or not the trial is to be masked, and the resources needed to perform the proper randomization-based permutational analysis. PMID:3203526

  18. The RAZOR (randomized open vs robotic cystectomy) trial: study design and trial update.

    PubMed

    Smith, Norm D; Castle, Erik P; Gonzalgo, Mark L; Svatek, Robert S; Weizer, Alon Z; Montgomery, Jeffrey S; Pruthi, Raj S; Woods, Michael E; Tollefson, Matthew K; Konety, Badrinath R; Shabsigh, Ahmad; Krupski, Tracey; Barocas, Daniel A; Dash, Atreya; Quek, Marcus L; Kibel, Adam S; Parekh, Dipen J

    2015-02-01

    The purpose of the RAZOR (randomized open vs robotic cystectomy) study is to compare open radical cystectomy (ORC) vs robot-assisted RC (RARC), pelvic lymph node dissection (PLND) and urinary diversion for oncological outcomes, complications and health-related quality of life (HRQL) measures with a primary endpoint of 2-year progression-free survival (PFS). RAZOR is a multi-institutional, randomized, non-inferior, phase III trial that will enrol at least 320 patients with T1-T4, N0-N1, M0 bladder cancer with ≈160 patients in both the RARC and ORC arms at 15 participating institutions. Data will be collected prospectively at each institution for cancer outcomes, complications of surgery and HRQL measures, and then submitted to trial data management services Cancer Research and Biostatistics (CRAB) for final analyses. To date, 306 patients have been randomized and accrual to the RAZOR trial is expected to conclude in 2014. In this study, we report the RAZOR trial experimental design, objectives, data safety, and monitoring, and accrual update. The RAZOR trial is a landmark study in urological oncology, randomizing T1-T4, N0-N1, M0 patients with bladder cancer to ORC vs RARC, PLND and urinary diversion. RAZOR is a multi-institutional, non-inferiority trial evaluating cancer outcomes, surgical complications and HRQL measures of ORC vs RARC with a primary endpoint of 2-year PFS. Full data from the RAZOR trial are not expected until 2016-2017. PMID:25626182

  19. Causal Mediation Analyses for Randomized Trials.

    PubMed

    Lynch, Kevin G; Cary, Mark; Gallop, Robert; Ten Have, Thomas R

    2008-01-01

    In the context of randomized intervention trials, we describe causal methods for analyzing how post-randomization factors constitute the process through which randomized baseline interventions act on outcomes. Traditionally, such mediation analyses have been undertaken with great caution, because they assume that the mediating factor is also randomly assigned to individuals in addition to the randomized baseline intervention (i.e., sequential ignorability). Because the mediating factors are typically not randomized, such analyses are unprotected from unmeasured confounders that may lead to biased inference. We review several causal approaches that attempt to reduce such bias without assuming that the mediating factor is randomized. However, these causal approaches require certain interaction assumptions that may be assessed if there is enough treatment heterogeneity with respect to the mediator. We describe available estimation procedures in the context of several examples from the literature and provide resources for software code. PMID:19484136

  20. The RAZOR (randomized open vs robotic cystectomy) trial: study design and trial update

    PubMed Central

    Smith, Norm D.; Castle, Erik P.; Gonzalgo, Mark L.; Svatek, Robert S.; Weizer, Alon Z.; Montgomery, Jeffrey S.; Pruthi, Raj S.; Woods, Michael E.; Tollefson, Matthew K.; Konety, Badrinath R.; Shabsigh, Ahmad; Krupski, Tracey; Barocas, Daniel A.; Dash, Atreya; Quek, Marcus L.; Kibel, Adam S.; Parekh, Dipen J.

    2016-01-01

    The purpose of the RAZOR (randomized open vs robotic cystectomy) study is to compare open radical cystectomy (ORC) vs robot-assisted RC (RARC), pelvic lymph node dissection (PLND) and urinary diversion for oncological outcomes, complications and health-related quality of life (HRQL) measures with a primary endpoint of 2-year progression-free survival (PFS). RAZOR is a multi-institutional, randomized, non-inferior, phase III trial that will enrol at least 320 patients with T1–T4, N0–N1, M0 bladder cancer with ≈160 patients in both the RARC and ORC arms at 15 participating institutions. Data will be collected prospectively at each institution for cancer outcomes, complications of surgery and HRQL measures, and then submitted to trial data management services Cancer Research and Biostatistics (CRAB) for final analyses. To date, 306 patients have been randomized and accrual to the RAZOR trial is expected to conclude in 2014. In this study, we report the RAZOR trial experimental design, objectives, data safety, and monitoring, and accrual update. The RAZOR trial is a landmark study in urological oncology, randomizing T1–T4, N0–N1, M0 patients with bladder cancer to ORC vs RARC, PLND and urinary diversion. RAZOR is a multi-institutional, non-inferiority trial evaluating cancer outcomes, surgical complications and HRQL measures of ORC vs RARC with a primary endpoint of 2-year PFS. Full data from the RAZOR trial are not expected until 2016–2017. PMID:25626182

  1. PCSK7 Genotype Modifies Effect of a Weight-Loss Diet on 2-Year Changes of Insulin Resistance: The POUNDS LOST Trial

    PubMed Central

    Huang, Tao; Huang, Jinyan; Qi, Qibin; Li, Yanping; Bray, George A.; Rood, Jennifer; Sacks, Frank M.

    2015-01-01

    OBJECTIVE A common variant rs236918 in the PCSK7 gene has the strongest association with iron homeostasis and is related to insulin resistance. Dietary carbohydrate (CHO) modulates the genetic effect on insulin resistance. We examined whether 2-year weight-loss diets modify the effect of PCSK7 genetic variants on changes in fasting insulin levels and insulin resistance in a randomized, controlled trial. RESEARCH DESIGN AND METHODS Data were analyzed in the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial, which is a randomized, controlled 2-year weight-loss trial using diets that differed in macronutrient proportions. PCSK7 rs236918 was genotyped in 730 overweight or obese adults (80% whites) in this trial. We assessed the progression in fasting insulin and glucose levels, and insulin resistance by genotypes. RESULTS During the 6-month weight-loss phase, the PCSK7 rs236918 G allele was significantly associated with greater decreases in fasting insulin levels in the high–dietary CHO group (P for interaction = 0.04), while the interaction for changes in HOMA-insulin resistance (HOMA-IR) (P for interaction = 0.06) did not reach significant levels in white subjects. The G allele was significantly associated with a greater decrease in fasting insulin levels and HOMA-IR in response to high dietary CHO levels (P = 0.02 and P = 0.03, respectively). From 6 months to 2 years (weight-regain phase), the interactions became attenuated due to the regaining of weight (P for interactions = 0.08 and 0.06, respectively). In addition, we observed similar and even stronger results in the whole-study samples from the trial. CONCLUSIONS Our data suggest that PCSK7 genotypes may interact with dietary CHO intake on changes in insulin sensitivity in the white Americans. PMID:25504030

  2. Recruiting Participants for Randomized Controlled Trials

    ERIC Educational Resources Information Center

    Gallagher, H. Alix; Roschelle, Jeremy; Feng, Mingyu

    2014-01-01

    The objective of this study was to look across strategies used in a wide range of studies to build a framework for researchers to use in conceptualizing the recruitment process. This paper harvests lessons learned across 19 randomized controlled trials in K-12 school settings conducted by a leading research organization to identify strategies that…

  3. Reporting Randomized Controlled Trials in Education

    ERIC Educational Resources Information Center

    Mayo-Wilson, Evan; Grant, Sean; Montgomery, Paul

    2014-01-01

    Randomized controlled trials (RCTs) are increasingly used to evaluate programs and interventions in order to inform education policy and practice. High quality reports of these RCTs are needed for interested readers to understand the rigor of the study, the interventions tested, and the context in which the evaluation took place (Mayo-Wilson et…

  4. New vertebral fractures after vertebroplasty: 2 year results from a randomised controlled trial

    PubMed Central

    Staples, MP; Howe, BM; Ringler, MD; Mitchell, P; Wriedt, CHR; Wark, JD; Ebeling, PR; Osborne, RH; Kallmes, DF; Buchbinder, R

    2015-01-01

    Purpose To assess the effect of vertebroplasty (VP) on the risk of further radiologically apparent vertebral fracture within two years of the procedure. Methods We conducted a randomised placebo-controlled trial of VP in people with acute osteoporotic vertebral fracture. Eligible participants were randomly assigned to VP (n=38) or placebo (n=40). Cement volume and leakage were recorded for the VP group. Plain thoracolumbar radiographs were taken at baseline, 12 and 24 months. Two independent radiologists assessed these for new and progressed fractures at the same, adjacent and non-adjacent levels. Results At 12 and 24 months, radiographs were available for 45 (58%) and 47 (60%) participants respectively. There were no between-group differences for new or progressed fractures: 32 and 40 in the VP group after 12 and 24 months compared with 21 and 33 in the placebo group (hazard ratio (HR) 1.80, 95% confidence interval (CI) 0.82 to 3.94). Similar results were seen when considering only adjacent (HR (95% CI): 2.30 (0.57 to 9.29)), and non-adjacent (HR (95% CI): 1.45 (0.55 to 3.81) levels. In all comparisons there was a consistent trend towards higher risk of any type of fracture in the group undergoing VP. Within the VP group, fracture risk was unrelated to total (HR (95% CI): 0.91 (0.71 to 1.17)) or relative (HR (95% CI): 1.31 (0.15 to 11.48)) cement volume, or cement leakage (HR (95% CI): 1.20 (0.63 to 2.31)). Conclusion For patients undergoing VP our study did not demonstrate significant increases in subsequent fracture risk beyond that experienced by those with vertebral fractures who did not undergo the procedure. However, because of the non-significant numerical increases observed, studies with adequate power are needed to draw definite conclusions about fracture risk. PMID:26272712

  5. Statistical properties of randomization in clinical trials.

    PubMed

    Lachin, J M

    1988-12-01

    This is the first of five articles on the properties of different randomization procedures used in clinical trials. This paper presents definitions and discussions of the statistical properties of randomization procedures as they relate to both the design of a clinical trial and the statistical analysis of trial results. The subsequent papers consider, respectively, the properties of simple (complete), permuted-block (i.e., blocked), and urn (adaptive biased-coin) randomization. The properties described herein are the probabilities of treatment imbalances and the potential effects on the power of statistical tests; the permutational basis for statistical tests; and the potential for experimental biases in the assessment of treatment effects due either to the predictability of the random allocations (selection bias) or the susceptibility of the randomization procedure to covariate imbalances (accidental bias). For most randomization procedures, the probabilities of overall treatment imbalances are readily computed, even when a stratified randomization is used. This is important because treatment imbalance may affect statistical power. It is shown, however, that treatment imbalance must be substantial before power is more than trivially affected. The differences between a population versus a permutation model as a basis for a statistical test are reviewed. It is argued that a population model can only be invoked in clinical trials as an untestable assumption, rather than being formally based on sampling at random from a population. On the other hand, a permutational analysis based on the randomization actually employed requires no assumptions regarding the origin of the samples of patients studied. The large sample permutational distribution of the family of linear rank tests is described as a basis for easily conducting a variety of permutation tests. Subgroup (stratified) analyses, analyses when some data are missing, and regression model analyses are also

  6. [Randomized clinical trials and real clinical practice].

    PubMed

    Heerlein, Andrés

    2009-01-01

    One of the emerging problems in modern medicine is that part of its highly efficacious treatments do not show significant effectiveness in real world systems of care. Efficacy studies address the appropriate dosages, short term response and feasibility of treatments in carefully selected populations, but they do not necessarily provide information for decisions in clinical practice. This review aims to present strengths and limitations of different methodological types of trials and to offer an overview of how knowledge from clinical trials can be used for clinical practice. The important effect of funding source on the outcome of randomized controlled trials is discussed. Some key questions in the treatment assessment of depression, schizophrenia and different medical conditions are discussed, with a focus on the possibilities and restrictions of translating clinical trial results into real-world settings. Empirical evidence shows that although randomized controlled trials are the gold standard for proving efficacy of a therapeutic procedure they often suffer from funding source bias and from lack of generalizability. Effectiveness studies evaluate effects of treatments under conditions approximating usual care. Another key area that can be addressed by effectiveness studies is the impact on important health policy measures such as disability days, days of work or medical costs, etc. Conclusions show that the future assessment of treatment regimes for clinical utility requires less biased efficacy studies and more effectiveness studies addressing major issues from all relevant perspectives. PMID:19543562

  7. Randomized controlled trials - a matter of design.

    PubMed

    Spieth, Peter Markus; Kubasch, Anne Sophie; Penzlin, Ana Isabel; Illigens, Ben Min-Woo; Barlinn, Kristian; Siepmann, Timo

    2016-01-01

    Randomized controlled trials (RCTs) are the hallmark of evidence-based medicine and form the basis for translating research data into clinical practice. This review summarizes commonly applied designs and quality indicators of RCTs to provide guidance in interpreting and critically evaluating clinical research data. It further reflects on the principle of equipoise and its practical applicability to clinical science with an emphasis on critical care and neurological research. We performed a review of educational material, review articles, methodological studies, and published clinical trials using the databases MEDLINE, PubMed, and ClinicalTrials.gov. The most relevant recommendations regarding design, conduction, and reporting of RCTs may include the following: 1) clinically relevant end points should be defined a priori, and an unbiased analysis and report of the study results should be warranted, 2) both significant and nonsignificant results should be objectively reported and published, 3) structured study design and performance as indicated in the Consolidated Standards of Reporting Trials statement should be employed as well as registration in a public trial database, 4) potential conflicts of interest and funding sources should be disclaimed in study report or publication, and 5) in the comparison of experimental treatment with standard care, preplanned interim analyses during an ongoing RCT can aid in maintaining clinical equipoise by assessing benefit, harm, or futility, thus allowing decision on continuation or termination of the trial. PMID:27354804

  8. Informed Consent and Cluster-Randomized Trials

    PubMed Central

    Dawson, Angus

    2012-01-01

    We argue that cluster-randomized trials are an important methodology, essential to the evaluation of many public health interventions. However, in the case of at least some cluster-randomized trials, it is not possible, or is incompatible with the aims of the study, to obtain individual informed consent. This should not necessarily be seen as an impediment to ethical approval, providing that sufficient justification is given for this omission. We further argue that it should be the institutional review board’s task to evaluate whether the protocol is sufficiently justified to proceed without consent and that this is preferable to any reliance on community consent or other means of proxy consent. PMID:22390511

  9. Treatment costs associated with interventional cancer clinical trials conducted at a single UK institution over 2 years (2009–2010)

    PubMed Central

    Liniker, E; Harrison, M; Weaver, J M J; Agrawal, N; Chhabra, A; Kingshott, V; Bailey, S; Eisen, T G G; Corrie, P G

    2013-01-01

    Background: The conduct of clinical trials should be an integral part of routine patient care. Treating patients in trials incurs additional costs over and above standard of care (SOC), but the extent of the cost burden is not known. We undertook a retrospective cost attribution analysis to quantitate the treatment costs associated with cancer clinical trial protocols conducted over a 2 year period. Methods: All patients entered into oncology (non-haematology) clinical trials involving investigational medicinal products in 2009 and 2010 in a single UK institution were identified. The trial protocols on which they were treated were analysed to identify the treatment costs for the experimental arm(s) of the trial and the equivalent SOC had the patient not been entered in the trial. The treatment cost difference was calculated by subtracting the experimental treatment cost from SOC cost. For randomised trials, an average treatment cost was estimated by taking into account the number of arms and randomisation ratio. An estimate of the annual treatment costs was calculated. Results: A total of 357 adult oncology patients were treated on 53 different trial protocols: 40 phase III, 2 randomised II/III and 11 phase II design. A total of 27 trials were academic, non-commercial sponsored trials and 26 were commercial sponsored trials. When compared with SOC, the average treatment cost per patient was an excess of £431 for a non-commercial trial (range £6393 excess to £6005 saving) and a saving of £9294 for a commercial trial (range £0 to £71 480). There was an overall treatment cost saving of £388 719 in 2009 and £496 556 in 2010, largely attributable to pharmaceutical company provision of free drug supplies. Conclusion: On an average, non-commercial trial protocols were associated with a small per patient excess treatment cost, whereas commercial trials were associated with a substantially higher cost saving. Taking into account the total number of patients

  10. Covariate-based constrained randomization of group-randomized trials.

    PubMed

    Moulton, Lawrence H

    2004-01-01

    Group-randomized study designs are useful when individually randomized designs are either not possible, or will not be able to estimate the parameters of interest. Blocked and/or stratified (for example, pair-matched) designs have been used, and their properties statistically evaluated by many researchers. Group-randomized trials often have small numbers of experimental units, and strong, geographically induced between-unit correlation, which increase the chance of obtaining a "bad" randomization outcome. This article describes a procedure--random selection from a list of acceptable allocations--to allocate treatment conditions in a way that ensures balance on relevant covariates. Numerous individual- and group-level covariates can be balanced using exact or caliper criteria. Simulation results indicate that this method has good frequency properties, but some care may be needed not to overly constrain the randomization. There is a trade-off between achieving good balance through a highly constrained design, and jeopardizing the appearance of impartiality of the investigator and potentially departing from the nominal Type I error. PMID:16279255

  11. Cluster randomized trials for pharmacy practice research.

    PubMed

    Gums, Tyler; Carter, Barry; Foster, Eric

    2016-06-01

    Introduction Cluster randomized trials (CRTs) are now the gold standard in health services research, including pharmacy-based interventions. Studies of behaviour, epidemiology, lifestyle modifications, educational programs, and health care models are utilizing the strengths of cluster randomized analyses. Methodology The key property of CRTs is the unit of randomization (clusters), which may be different from the unit of analysis (individual). Subject sample size and, ideally, the number of clusters is determined by the relationship of between-cluster and within-cluster variability. The correlation among participants recruited from the same cluster is known as the intraclass correlation coefficient (ICC). Generally, having more clusters with smaller ICC values will lead to smaller sample sizes. When selecting clusters, stratification before randomization may be useful in decreasing imbalances between study arms. Participant recruitment methods can differ from other types of randomized trials, as blinding a behavioural intervention cannot always be done. When to use CRTs can yield results that are relevant for making "real world" decisions. CRTs are often used in non-therapeutic intervention studies (e.g. change in practice guidelines). The advantages of CRT design in pharmacy research have been avoiding contamination and the generalizability of the results. A large CRT that studied physician-pharmacist collaborative management of hypertension is used in this manuscript as a CRT example. The trial, entitled Collaboration Among Pharmacists and physicians To Improve Outcomes Now (CAPTION), was implemented in primary care offices in the United States for hypertensive patients. Limitations CRT design limitations include the need for a large number of clusters, high costs, increased training, increased monitoring, and statistical complexity. PMID:26715549

  12. Myopia Control with a Novel Peripheral Gradient Soft Lens and Orthokeratology: A 2-Year Clinical Trial

    PubMed Central

    Pauné, Jaime; Morales, Hari; Armengol, Jesús; Quevedo, Lluisa; Faria-Ribeiro, Miguel; González-Méijome, José M.

    2015-01-01

    Objective. To evaluate the degree of axial elongation with soft radial refractive gradient (SRRG) contact lenses, orthokeratology (OK), and single vision (SV) spectacle lenses (control) during a period of 1 year before treatment and 2 years after treatment. Methods. This was a prospective, longitudinal, nonrandomized study. The study groups consisted of 30, 29, and 41 children, respectively. The axial length (AL) was measured during 2 years after recruitment and lens fitting. Results. The baseline refractive sphere was correlated significantly (Spearman's Rho (ρ) correlation = 0.542; P < 0.0001) with the amount of myopia progression before baseline. After 2 years, the mean myopia progression values for the SRRG, OK, and SV groups were −0.56 ± 0.51, −0.32 ± 0.53, and −0.98 ± 0.58 diopter, respectively. The results represent reductions in myopic progression of 43% and 67% for the SRRG and OK groups, respectively, compared to the SV group. The AL increased 27% and 38% less in the SRRG and OK groups, respectively compared with the SV group at the 2-year visit (P < 0.05). Axial elongation was not significantly different between SRRG and OK (P = 0.430). Conclusion. The SRRG lens significantly decreased AL elongation compared to the SV control group. The SRRG lens was similarly effective to OK in preventing myopia progression in myopic children and adolescent. PMID:26605331

  13. Alcohol Prevention and School Students: Findings from an Australian 2-Year Trial of Integrated Harm Minimization School Drug Education

    ERIC Educational Resources Information Center

    Midford, Richard; Ramsden, Robyn; Lester, Leanne; Cahill, Helen; Mitchell, Johanna; Foxcroft, David R.; Venning, Lynne

    2014-01-01

    The Drug Education in Victorian Schools program provided integrated education about licit and illicit drugs, employed a harm minimization approach that incorporated participatory, critical thinking and skill-based teaching methods, and engaged parental influence through home activities. A cluster-randomized, controlled trial of the program was…

  14. Effects of galantamine in a 2-year, randomized, placebo-controlled study in Alzheimer’s disease

    PubMed Central

    Hager, Klaus; Baseman, Alan S; Nye, Jeffrey S; Brashear, H Robert; Han, John; Sano, Mary; Davis, Bonnie; Richards, Henry M

    2014-01-01

    Background Currently available treatments for Alzheimer’s disease (AD) can produce mild improvements in cognitive function, behavior, and activities of daily living in patients, but their influence on long-term survival is not well established. This study was designed to assess patient survival and drug efficacy following a 2-year galantamine treatment in patients with mild to moderately severe AD. Methods In this multicenter, double-blind study, patients were randomized 1:1 to receive galantamine or placebo. One primary end point was safety; mortality was assessed. An independent Data Safety Monitoring Board monitored mortality for the total deaths reaching prespecified numbers, using a time-to-event method and a Cox-regression model. The primary efficacy end point was cognitive change from baseline to month 24, as measured by the Mini-Mental State Examination (MMSE) score, analyzed using intent-to-treat analysis with the ‘last observation carried forward’ approach, in an analysis of covariance model. Results In all, 1,024 galantamine- and 1,021 placebo-treated patients received study drug, with mean age ~73 years, and mean (standard deviation [SD]) baseline MMSE score of 19 (4.08). A total of 32% of patients (661/2,045) completed the study, 27% (554/2,045) withdrew, and 41% (830/2,045) did not complete the study and were discontinued due to a Data Safety Monitoring Board-recommended early study termination. The mortality rate was significantly lower in the galantamine group versus placebo (hazard ratio [HR] =0.58; 95% confidence interval [CI]: 0.37; 0.89) (P=0.011). Cognitive impairment, based on the mean (SD) change in MMSE scores from baseline to month 24, significantly worsened in the placebo (−2.14 [4.34]) compared with the galantamine group (−1.41 [4.05]) (P<0.001). Functional impairment, based on mean (SD) change in the Disability Assessment in Dementia score (secondary end point), at month 24 significantly worsened in the placebo (−10.81 [18

  15. Translating theory into practice: results of a 2-year trial for the LEAD programme.

    PubMed

    Shelton, D

    2008-05-01

    This paper presents data for 2 years of a continuing study aimed to reduce the risk of first-time involvement by minority youth with the juvenile justice system. A quasi-experimental design was used to test a 14-week expressive art curriculum (LEAD: leadership, education, achievement and development) implemented in two rural communities. A total of 70 African American youth participated in the programme over a 2-year period. Pre- and post-test differences were examined for protective factors, behavioural self-control, self-esteem and resilience measures. When compared with the after-school programme (control group), youth in the LEAD programme in both communities had more dramatic increases in post-test scores following the intervention. The combined data from year 1 and year 2 provide positive findings in support of LEAD as a prevention programme for young offenders. The placement of the programme within an African American church in year 2 improved the processes of the LEAD programme and seemed to provide a better fit with the original design of the programme, highlighting the importance of the context, in which the programme was provided. PMID:18387150

  16. A randomised trial of granulocyte-macrophage colony-stimulating factor for neonatal sepsis: outcomes at 2 years

    PubMed Central

    Marlow, Neil; Morris, Timothy; Brocklehurst, Peter; Carr, Robert; Cowan, Frances M; Patel, Nishma; Petrou, Stavros; Redshaw, Maggie E; Modi, Neena; Dore, Caroline

    2013-01-01

    Objective The authors performed a randomised trial in very preterm small-for-gestational age (SGA) babies to determine if prophylaxis with granulocyte-macrophage colony-stimulating factor (GM-CSF) improves outcomes (the PROGRAMS trial). Despite increased neutrophil counts following GM-CSF, the authors reported no significant difference in neonatal sepsis-free survival. Patients and methods 280 babies born <31 weeks of gestation and SGA were entered into the trial. Outcome was determined at 2 years to determine neurodevelopmental and general health outcomes, including economic costs. Results The authors found no significant differences in health outcomes or health and social care costs between the trial groups. In the GM-CSF arm, 87 of 134 (65%) babies survived to 2 years without severe disability compared with 87 of 131 (66%) controls (RR: 1·0, 95% CI 0·8 to 1·2). Marginally, more children receiving GM-CSF were reported to have cough (RR 1·7, 95% CI 1·1 to 2·6) and had signs of chronic respiratory disease (Harrison's sulcus; RR 2·0, 95% CI 1·0 to 3·9) though this was not reflected in bronchodilator use or need for hospitalisation for respiratory disease. Overall, the rate of neurologic abnormality (7%–9%) was similar but mean overall developmental scores were lower than expected for gestational age. Conclusions The administration of GM-CSF to very preterm SGA babies is not associated with improved or more adverse outcomes at 2 years of age. The apparent excess of developmental impairment in the entire PROGRAMS cohort, without corresponding increase in neurological abnormality, may represent diffuse brain injury attributable to intrauterine growth restriction. PMID:22542709

  17. Defocus Incorporated Soft Contact (DISC) lens slows myopia progression in Hong Kong Chinese schoolchildren: a 2-year randomised clinical trial

    PubMed Central

    Lam, Carly Siu Yin; Tang, Wing Chun; Tse, Dennis Yan-Yin; Tang, Ying Yung; To, Chi Ho

    2014-01-01

    Aims To determine if ‘Defocus Incorporated Soft Contact’ (DISC) lens wear slows childhood myopia progression. Methods A 2-year double-blind randomised controlled trial was carried out in 221 children aged 8–13 years, with myopia between −1.00 and −5.00 Dioptres (D) and astigmatism ≤1.00 D. Subjects were randomly assigned to the DISC (n=111) or single vision (SV; n=110) contact lens group. DISC lenses incorporated concentric rings, which provided an addition of +2.50 D, alternating with the normal distance correction. Refractive error (cycloplegic autorefraction) and axial length were measured at 6-month intervals. Differences between groups were analysed using unpaired t test. Results In total, 128 children completed the study, n=65 in the DISC group and n=63 in the SV group. Myopia progressed 25% more slowly for children in the DISC group compared with those in the control group (0.30 D/year; 95% CI −0.71 to −0.47 vs 0.4 D/year; 95% CI −0.93 to −0.65, p=0.031). Likewise, there was less axial elongation for children in the DISC versus SV groups (0.13 mm/year; 95% CI 0.20 to 0.31 vs 0.18 mm/year; 95% CI 0.30 to 0.43, p=0.009). Treatment effect correlated positively with DISC lens wearing time (r=0.342; p=0.005). Indeed, myopia in children who wore the DISC lenses for five or more hours/day progressed 46% (mean difference=−0.382 D, p=0.001; 95% CI −0.59 to −0.17) less than those in the SV group. Conclusions The daily wearing of DISC lens significantly slowed myopia progression and axial elongation in Hong Kong schoolchildren. The findings demonstrated that simultaneous clear vision with constant myopic defocus can retard myopia progression. PMID:24169657

  18. The penumbra of randomized control trials

    PubMed Central

    Nanivadekar, Arun S.

    2013-01-01

    Pre-occupation with randomized control trials as the basis of evidence-based medicine has increasingly shadowed other study designs over the last half a century. These include surveys, case-control studies, and case-cohort studies. They have the potential to overcome several ethical and cost constraints, but depend on the embedding of research in routine practice, emphasis on relevant but limited, accurate, and complete data, harnessing of information technology for this purpose, and epidemiological and statistical literacy among clinicians. Only then will it be possible to nurture and network research-oriented practices by therapeutic areas. Given these, the alternative study designs can pave the way to regulatory reforms that will ultimately benefit the discoverers, approvers and users of health-care tools. PMID:24010055

  19. A Framework for Designing Cluster Randomized Trials with Binary Outcomes

    ERIC Educational Resources Information Center

    Spybrook, Jessaca; Martinez, Andres

    2011-01-01

    The purpose of this paper is to provide a frame work for approaching a power analysis for a CRT (cluster randomized trial) with a binary outcome. The authors suggest a framework in the context of a simple CRT and then extend it to a blocked design, or a multi-site cluster randomized trial (MSCRT). The framework is based on proportions, an…

  20. ADULTS: A RANDOMIZED CONTROLLED CLINICAL TRIAL

    PubMed Central

    Shah, Krupa N.; Majeed, Zahraa; Yoruk, Yilmaz B.; Yang, Hongmei; Hilton, Tiffany N.; McMahon, James M.; Hall, William J.; Walck, Donna; Luque, Amneris E.; Ryan, Richard M.

    2016-01-01

    Objective HIV-infected older adults (HOA) are at risk of functional decline. Interventions promoting physical activity that can attenuate functional decline and are easily translated into the HOA community are of high priority. We conducted a randomized, controlled clinical trial to evaluate whether a physical activity counseling intervention based on self-determination theory (SDT) improves physical function, autonomous motivation, depression and the quality of life (QOL) in HOA. Methods A total of 67 community-dwelling HOA with mild-to-moderate functional limitations were randomized to one of two groups: a physical activity counseling group or the usual care control group. We used SDT to guide the development of the experimental intervention. Outcome measures that were collected at baseline and final study visits included a battery of physical function tests, levels of physical activity, autonomous motivation, depression, and QOL. Results The study participants were similar in their demographic and clinical characteristics in both the treatment and control groups. Overall physical performance, gait speed, measures of endurance and strength, and levels of physical activity improved in the treatment group compared to the control group (p<0.05). Measures of autonomous regulation such as identified regulation, and measures of depression and QOL improved significantly in the treatment group compared to the control group (p<0.05). Across the groups, improvement in intrinsic regulation and QOL correlated with an improvement in physical function (p<0.05). Conclusion Our findings suggest that a physical activity counseling program grounded in SDT can improve physical function, autonomous motivation, depression, and QOL in HOA with functional limitations. PMID:26867045

  1. Randomized controlled trials: what are they and who needs them?

    PubMed

    Pihlstrom, Bruce L; Curran, Alice E; Voelker, Helen T; Kingman, Albert

    2012-06-01

    Dentistry is rapidly entering a new era of evidence-based practice, and society is demanding prevention and treatment that has been proven to be effective in terms of meaningful health outcomes. Practitioners, individual patients and the public need randomized controlled trials because they provide the highest level of scientific evidence to change clinical practice and inform public health policy. Well-designed randomized controlled trials are conceptually simple but deceptively complex to design, implement and translate into clinical practice. Randomized controlled trials are fundamentally different from observational clinical research because they randomly assign volunteers to receive test or control interventions, they are prospective and the success of the test intervention is based on a meaningful clinical outcome that is specified before the trial begins. To be successful, randomized controlled trials must be carefully designed and powered to answer a specific question that will be generalizable to the population under study. Randomized controlled trials can be designed to evaluate efficacy, effectiveness, superiority, equivalence or noninferiority. Prominent issues and challenges in designing and conducting randomized controlled trials include carefully defining enrollment criteria, establishing an organizational infrastructure, use of a data-coordinating center, developing a manual of procedures, obtaining informed consent, recruiting and ensuring the safety of volunteer subjects, ensuring data quality, analysis and publication of trial outcomes, and translating results into clinical practice. PMID:22507057

  2. Community based intervention to optimize osteoporosis management: randomized controlled trial

    PubMed Central

    2010-01-01

    Background Osteoporosis-related fractures are a significant public health concern. Interventions that increase detection and treatment of osteoporosis are underutilized. This pragmatic randomised study was done to evaluate the impact of a multifaceted community-based care program aimed at optimizing evidence-based management in patients at risk for osteoporosis and fractures. Methods This was a 12-month randomized trial performed in Ontario, Canada. Eligible patients were community-dwelling, aged ≥55 years, and identified to be at risk for osteoporosis-related fractures. Two hundred and one patients were allocated to the intervention group or to usual care. Components of the intervention were directed towards primary care physicians and patients and included facilitated bone mineral density testing, patient education and patient-specific recommendations for osteoporosis treatment. The primary outcome was the implementation of appropriate osteoporosis management. Results 101 patients were allocated to intervention and 100 to control. Mean age of participants was 71.9 ± 7.2 years and 94% were women. Pharmacological treatment (alendronate, risedronate, or raloxifene) for osteoporosis was increased by 29% compared to usual care (56% [29/52] vs. 27% [16/60]; relative risk [RR] 2.09, 95% confidence interval [CI] 1.29 to 3.40). More individuals in the intervention group were taking calcium (54% [54/101] vs. 20% [20/100]; RR 2.67, 95% CI 1.74 to 4.12) and vitamin D (33% [33/101] vs. 20% [20/100]; RR 1.63, 95% CI 1.01 to 2.65). Conclusions A multi-faceted community-based intervention improved management of osteoporosis in high risk patients compared with usual care. Trial Registration This trial has been registered with clinicaltrials.gov (ID: NCT00465387) PMID:20799973

  3. Effectiveness Trial of an Indicated Cognitive-Behavioral Group Adolescent Depression Prevention Program versus Bibliotherapy and Brochure Control at 1- and 2-Year Follow-Up

    PubMed Central

    Rohde, Paul; Stice, Eric; Shaw, Heather; Gau, Jeff M.

    2015-01-01

    Objective Evaluate the longterm effects of a brief group cognitive-behavioral (CB) adolescent depression indicated prevention program through 2-year follow-up, relative to CB bibliotherapy and brochure control, when high school personnel recruited students and delivered the program. Method 378 adolescents (M age = 15.5, SD = 1.2; 68% female, 72% White) with elevated self-assessed depressive symptoms who were randomized to CB group, CB bibliotherapy, or educational brochure control were assessed at pre, post, 6-, 12-, 18-, and 24-month follow-up. Results By 2 years post-intervention, CB group participants showed significantly lower major depressive disorder (MDD) onset versus CB bibliotherapy (10% vs. 25%, respectively; HR = 2.48, p = .006), but the incidence difference relative to brochure controls (17%) was nonsignificant; MDD incidence for bibliotherapy and brochure controls did not differ. Although CB group participants showed lower depressive symptoms at post versus brochure controls, there were no effects for this outcome or for social adjustment or substance use over 2-year follow-up. Moderator analyses suggested that participants with higher baseline depressive symptoms showed greater longterm symptom reductions in the CB group intervention versus bibliotherapy. Conclusions The evidence that a brief CB group intervention delivered by real-world providers significantly reduced MDD onset versus CB bibliotherapy is potentially encouraging. However, the lack of MDD prevention effects relative to brochure control and lack of longterm symptom effects (though consistent with results from other depression prevention trials), suggest that the delivery of CB group should be refined to strengthen its effectiveness. PMID:25894666

  4. Pragmatic design in randomized controlled trials.

    PubMed

    Purgato, M; Barbui, C; Stroup, S; Adams, C

    2015-01-01

    At more than 10 years after the paper by Hotopf and colleagues regarding pragmatic trials in psychiatry, the field has evolved and is evolving further. There have been many developments in our understanding of what pragmatism really means, and excellent examples of truly pragmatic trials in psychiatry are currently available. Funders have helped encourage more emphasis on the need for such studies, but 'local' and trans-national regulations could help more. Consumers of the evidence should have a greater voice in generating the research agenda and, as this happens, the questions generated are more likely to be answered by a pragmatic approach to trials. PMID:25065958

  5. Analytic Methods for Individually Randomized Group Treatment Trials and Group-Randomized Trials When Subjects Belong to Multiple Groups

    PubMed Central

    Andridge, Rebecca. R.; Shoben, Abigail B.; Muller, Keith E.; Murray, David M.

    2014-01-01

    Participants in trials may be randomized either individually or in groups, and may receive their treatment either entirely individually, entirely in groups, or partially individually and partially in groups. This paper concerns cases in which participants receive their treatment either entirely or partially in groups, regardless of how they were randomized. Participants in Group-Randomized Trials (GRTs) are randomized in groups and participants in Individually Randomized Group Treatment (IRGT) trials are individually randomized, but participants in both types of trials receive part or all of their treatment in groups or through common change agents. Participants who receive part or all of their treatment in a group are expected to have positively correlated outcome measurements. This paper addresses a situation that occurs in GRTs and IRGT trials – participants receive treatment through more than one group. As motivation, we consider trials in The Childhood Obesity Prevention and Treatment Research Consortium (COPTR), in which each child participant receives treatment in at least two groups. In simulation studies we considered several possible analytic approaches over a variety of possible group structures. A mixed model with random effects for both groups provided the only consistent protection against inflated type I error rates and did so at the cost of only moderate loss of power when intraclass correlations were not large. We recommend constraining variance estimates to be positive and using the Kenward-Roger adjustment for degrees of freedom; this combination provided additional power but maintained type I error rates at the nominal level. PMID:24399701

  6. European randomized lung cancer screening trials: Post NLST.

    PubMed

    Field, John K; van Klaveren, Rob; Pedersen, Jesper H; Pastorino, Ugo; Paci, Eugino; Becker, Nikolauss; Infante, Maurizo; Oudkerk, Matthijs; de Koning, Harry J

    2013-10-01

    Overview of the European randomized lung cancer CT screening trials (EUCT) is presented with regard to the implementation of CT screening in Europe; post NLST. All seven principal investigators completed a questionnaire on the epidemiological, radiological, and nodule management aspects of their trials at August 2010, which included 32,000 people, inclusion of UKLS pilot trial will reach 36,000. An interim analysis is planned, but the final mortality data testing is scheduled for 2015. PMID:23893464

  7. Triangular Titanium Implants for Minimally Invasive Sacroiliac Joint Fusion: 2-Year Follow-Up from a Prospective Multicenter Trial

    PubMed Central

    Bitan, Fabien; Lockstadt, Harry; Kovalsky, Don; Cher, Daniel; Hillen, Travis

    2016-01-01

    quality of life at 2 years. Imaging showed that bone apposition to implants was common but radiographic evidence of intraarticular fusion within the joint may take more than 1 year in many patients. This prospective multicenter clinical trial was approved by local or regional IRBs at each center prior to first patient enrollment. Informed consent with IRB-approved study-specific consent forms was obtained from all patients prior to participation. PMID:27162715

  8. Estimating the Causal Effect of Randomization versus Treatment Preference in a Doubly Randomized Preference Trial

    ERIC Educational Resources Information Center

    Marcus, Sue M.; Stuart, Elizabeth A.; Wang, Pei; Shadish, William R.; Steiner, Peter M.

    2012-01-01

    Although randomized studies have high internal validity, generalizability of the estimated causal effect from randomized clinical trials to real-world clinical or educational practice may be limited. We consider the implication of randomized assignment to treatment, as compared with choice of preferred treatment as it occurs in real-world…

  9. Summer School Effects in a Randomized Field Trial

    ERIC Educational Resources Information Center

    Zvoch, Keith; Stevens, Joseph J.

    2013-01-01

    This field-based randomized trial examined the effect of assignment to and participation in summer school for two moderately at-risk samples of struggling readers. Application of multiple regression models to difference scores capturing the change in summer reading fluency revealed that kindergarten students randomly assigned to summer school…

  10. Power Calculations for Binary Moderator in Cluster Randomized Trials

    ERIC Educational Resources Information Center

    Spybrook, Jessaca; Kelcey, Ben

    2014-01-01

    Cluster randomized trials (CRTs), or studies in which intact groups of individuals are randomly assigned to a condition, are becoming more common in the evaluation of educational programs, policies, and practices. The website for the National Center for Education Evaluation and Regional Assistance (NCEE) reveals they have launched over 30…

  11. Perceptions of Massage Therapists Participating in a Randomized Controlled Trial

    PubMed Central

    Perlman, Adam; Dreusicke, Mark; Keever, Teresa; Ali, Ather

    2015-01-01

    Background Clinical practice and randomized trials often have disparate aims, despite involving similar interventions. Attitudes and expectancies of practitioners influence patient outcomes, and there is growing emphasis on optimizing provider–patient relationships. In this study, we evaluated the experiences of licensed massage therapists involved in a randomized controlled clinical trial using qualitative methodology. Methods Seven massage therapists who were interventionists in a randomized controlled trial participated in structured interviews approximately 30 minutes in length. Interviews focused on their experiences and perceptions regarding aspects of the clinical trial, as well as recommendations for future trials. Transcribed interviews were analyzed for emergent topics and themes using standard qualitative methods. Results Six themes emerged. Therapists discussed 1) promoting the profession of massage therapy through research, 2) mixed views on using standardized protocols, 3) challenges of sham interventions, 4) participant response to the sham intervention, 5) views on scheduling and compensation, and 6) unanticipated benefits of participating in research. Conclusions Therapists largely appreciated the opportunity to promote massage through research. They demonstrated insight and understanding of the rationale for a clinical trial adhering to a standardized protocol. Evaluating the experiences and ideas of complementary and alternative medicine practitioners provides valuable insight that is relevant for the implementation and design of randomized trials. PMID:26388961

  12. High School Students with Reading Comprehension Difficulties: Results of a Randomized Control Trial of a Two-Year Reading Intervention

    ERIC Educational Resources Information Center

    Vaughn, Sharon; Roberts, Greg; Wexler, Jade; Vaughn, Michael G.; Fall, Anna-Mária; Schnakenberg, Jennifer B.

    2015-01-01

    A 2-year, randomized control trial with 9th to 10th grade students with significant reading problems was provided for 50 minutes a day in small groups. Comparison students were provided an elective class and treatment students the reading intervention. Students were identified as demonstrating reading difficulties through failure on their state…

  13. Methods for sample size determination in cluster randomized trials

    PubMed Central

    Rutterford, Clare; Copas, Andrew; Eldridge, Sandra

    2015-01-01

    Background: The use of cluster randomized trials (CRTs) is increasing, along with the variety in their design and analysis. The simplest approach for their sample size calculation is to calculate the sample size assuming individual randomization and inflate this by a design effect to account for randomization by cluster. The assumptions of a simple design effect may not always be met; alternative or more complicated approaches are required. Methods: We summarise a wide range of sample size methods available for cluster randomized trials. For those familiar with sample size calculations for individually randomized trials but with less experience in the clustered case, this manuscript provides formulae for a wide range of scenarios with associated explanation and recommendations. For those with more experience, comprehensive summaries are provided that allow quick identification of methods for a given design, outcome and analysis method. Results: We present first those methods applicable to the simplest two-arm, parallel group, completely randomized design followed by methods that incorporate deviations from this design such as: variability in cluster sizes; attrition; non-compliance; or the inclusion of baseline covariates or repeated measures. The paper concludes with methods for alternative designs. Conclusions: There is a large amount of methodology available for sample size calculations in CRTs. This paper gives the most comprehensive description of published methodology for sample size calculation and provides an important resource for those designing these trials. PMID:26174515

  14. Randomized controlled trials in diving and hyperbaric medicine.

    PubMed

    Bennett, Michael H

    2013-01-01

    Randomized controlled trials (RCTs) are widely accepted as the most appropriate methodology available for the investigation of health interventions. This is because of the low potential for systematic bias and the ability to assume causality. Well-designed RCTs, often modified by the addition of blinding participants to the treatment allocated, greatly assist physicians and funding agencies in deciding on the most effective and cost-efficient methods available to prevent and treat ill health. One of the problems for hyperbaric physicians is the widely scattered nature of the evidence, making retrieval and appraisal problematic. This review assembles the randomized evidence in order to assist practitioners, discusses the nature of randomized trials and explores approaches to designing and performing powerful and convincing trials in this area. It is extracted from the UHMS Report Hyperbaric Oxygen Therapy Indications. PMID:24224286

  15. A randomized clinical trial of lithium in multiple system atrophy.

    PubMed

    Saccà, Francesco; Marsili, Angela; Quarantelli, Mario; Brescia Morra, Vincenzo; Brunetti, Arturo; Carbone, Rosa; Pane, Chiara; Puorro, Giorgia; Russo, Cinzia Valeria; Salvatore, Elena; Tucci, Tecla; De Michele, Giuseppe; Filla, Alessandro

    2013-02-01

    The aim of our study was to test the safety and tolerability of lithium in multiple system atrophy (MSA). The study was randomized, placebo-controlled, and double-blind. The primary endpoint of the study was safety and tolerability. An interim analysis, performed 1 year after the first patient was randomized, showed a higher proportion of trial abandon (P < 0.01) and a higher number of adverse events (P < 0.02) in the lithium group. The trial was stopped by the Data Monitoring Committee. Overall, lithium was not well tolerated, and we do not encourage future studies with lithium in MSA patients. PMID:22932748

  16. Randomized Controlled Trials for the Treatment of Hidradenitis Suppurativa.

    PubMed

    van Rappard, Dominique C; Mekkes, Jan R; Tzellos, Thrasivoulos

    2016-01-01

    Hidradenitis suppurativa (HS) is a chronic, inflammatory, recurrent, debilitating skin disease. Several treatment modalities are available, but most of them lack high-quality evidence. A systematic search was performed to identify all randomized controlled trials for the treatment of HS in order to review and evaluate the evidence. Recommendations for future randomized controlled trials include using validated scores, inclusion of patient rated outcomes, and thorough report of side effects. Evidence for long-term treatment and benefit/risk ratio of available treatment modalities is needed in order to enhance evidence-based treatment in daily clinical practice. Combining surgery with antiinflammatory treatment warrants further investigation. PMID:26617360

  17. RANDOMIZED CONTROLLED CLINICAL TRIALS IN ORTHOPEDICS: DIFFICULTIES AND LIMITATIONS

    PubMed Central

    Malavolta, Eduardo Angeli; Demange, Marco Kawamura; Gobbi, Riccardo Gomes; Imamura, Marta; Fregni, Felipe

    2015-01-01

    Randomized controlled clinical trials (RCTs) are considered to be the gold standard for evidence-based medicine nowadays, and are important for directing medical practice through consistent scientific observations. Steps such as patient selection, randomization and blinding are fundamental for conducting a RCT, but some additional difficulties are presented in trials that involve surgical procedures, as is common in orthopedics. The aim of this article was to highlight and discuss some difficulties and possible limitations on RCTs within the field of surgery. PMID:27027037

  18. A multiple imputation strategy for sequential multiple assignment randomized trials.

    PubMed

    Shortreed, Susan M; Laber, Eric; Scott Stroup, T; Pineau, Joelle; Murphy, Susan A

    2014-10-30

    Sequential multiple assignment randomized trials (SMARTs) are increasingly being used to inform clinical and intervention science. In a SMART, each patient is repeatedly randomized over time. Each randomization occurs at a critical decision point in the treatment course. These critical decision points often correspond to milestones in the disease process or other changes in a patient's health status. Thus, the timing and number of randomizations may vary across patients and depend on evolving patient-specific information. This presents unique challenges when analyzing data from a SMART in the presence of missing data. This paper presents the first comprehensive discussion of missing data issues typical of SMART studies: we describe five specific challenges and propose a flexible imputation strategy to facilitate valid statistical estimation and inference using incomplete data from a SMART. To illustrate these contributions, we consider data from the Clinical Antipsychotic Trial of Intervention and Effectiveness, one of the most well-known SMARTs to date. PMID:24919867

  19. Efficacy Trial of a Selective Prevention Program Targeting Both Eating Disorders and Obesity among Female College Students: 1- and 2-Year Follow-Up Effects

    ERIC Educational Resources Information Center

    Stice, Eric; Rohde, Paul; Shaw, Heather; Marti, C. Nathan

    2013-01-01

    Objective: Evaluate the effects of a prevention program targeting both eating disorders and obesity at 1- and 2-year follow-ups. Method: Female college students at risk for these outcomes because of body image concerns (N = 398) were randomized to the "Healthy Weight 2" group-based 4-hr prevention program, which promotes lasting healthy…

  20. Hypnotherapy in radiotherapy patients: A randomized trial

    SciTech Connect

    Stalpers, Lukas J.A. . E-mail: l.stalpers@amc.uva.nl; Costa, Hanna C. da; Merbis, Merijn A.E.; Fortuin, Andries A.; Muller, Martin J.; Dam, Frits van

    2005-02-01

    Purpose: To determine whether hypnotherapy reduces anxiety and improves the quality of life in cancer patients undergoing curative radiotherapy (RT). Methods and materials: After providing written informed consent, 69 patients were randomized between standard curative RT alone (36 controls) and RT plus hypnotherapy (33 patients). Patients in the hypnotherapy group received hypnotherapy at the intake, before RT simulation, before the first RT session, and halfway between the RT course. Anxiety was evaluated by the State-Trait Anxiety Inventory DY-1 form at six points. Quality of life was measured by the Rand Medical Outcomes Study 36-item Health Survey (SF-36) at five points. Additionally, patients answered a questionnaire to evaluate their experience and the possible benefits of this research project. Results: No statistically significant difference was found in anxiety or quality of life between the hypnotherapy and control groups. However, significantly more patients in the hypnotherapy group indicated an improvement in mental (p < 0.05) and overall (p < 0.05) well-being. Conclusion: Hypnotherapy did not reduce anxiety or improve the quality of life in cancer patients undergoing curative RT. The absence of statistically significant differences between the two groups contrasts with the hypnotherapy patients' own sense of mental and overall well-being, which was significantly greater after hypnotherapy. It cannot be excluded that the extra attention by the hypnotherapist was responsible for this beneficial effect in the hypnotherapy group. An attention-only control group would be necessary to control for this effect.

  1. In School Settings, Are All RCTs (Randomized Control Trials) Exploratory?

    ERIC Educational Resources Information Center

    Newman, Denis; Jaciw, Andrew P.

    2012-01-01

    The motivation for this paper is the authors' recent work on several randomized control trials in which they found the primary result, which averaged across subgroups or sites, to be moderated by demographic or site characteristics. They are led to examine a distinction that the Institute of Education Sciences (IES) makes between "confirmatory"…

  2. A Randomized Controlled Trial of Two Online Mathematics Curricula

    ERIC Educational Resources Information Center

    Wang, Haiwen; Woodworth, Katrina

    2011-01-01

    This study applies a randomized controlled trial to examine the effects of supplemental instruction using two online mathematics curricula--DreamBox and Reasoning Mind. It is an independent evaluation intended to generate unbiased results that will help inform the ongoing development of a charter school network's hybrid instructional model, which…

  3. Affectionate Writing Reduces Total Cholesterol: Two Randomized, Controlled Trials

    ERIC Educational Resources Information Center

    Floyd, Kory; Mikkelson, Alan C.; Hesse, Colin; Pauley, Perry M.

    2007-01-01

    In two 5-week trials, healthy college students were randomly assigned either to experimental or control groups. Participants in the experimental groups wrote about their affection for significant friends, relatives, and/or romantic partners for 20 minutes on three separate occasions; on the same schedule, those in the control groups wrote about…

  4. Improved Cardiovascular Prevention Using Best CME Practices: A Randomized Trial

    ERIC Educational Resources Information Center

    Laprise, Rejean; Thivierge, Robert; Gosselin, Gilbert; Bujas-Bobanovic, Maja; Vandal, Sylvie; Paquette, Daniel; Luneau, Micheline; Julien, Pierre; Goulet, Serge; Desaulniers, Jean; Maltais, Paule

    2009-01-01

    Introduction: It was hypothesized that after a continuing medical education (CME) event, practice enablers and reinforcers addressing main clinical barriers to preventive care would be more effective in improving general practitioners' (GPs) adherence to cardiovascular guidelines than a CME event only. Methods: A cluster-randomized trial was…

  5. A Multisite Cluster Randomized Field Trial of Open Court Reading

    ERIC Educational Resources Information Center

    Borman, Geoffrey D.; Dowling, N. Maritza; Schneck, Carrie

    2008-01-01

    In this article, the authors report achievement outcomes of a multisite cluster randomized field trial of Open Court Reading 2005 (OCR), a K-6 literacy curriculum published by SRA/McGraw-Hill. The participants are 49 first-grade through fifth-grade classrooms from predominantly minority and poor contexts across the nation. Blocking by grade level…

  6. Promoting Healthy Weight with "Stability Skills First": A Randomized Trial

    ERIC Educational Resources Information Center

    Kiernan, Michaela; Brown, Susan D.; Schoffman, Danielle E.; Lee, Katherine; King, Abby C.; Taylor, C. Barr; Schleicher, Nina C.; Perri, Michael G.

    2013-01-01

    Objective: Although behavioral weight-loss interventions produce short-term weight loss, long-term maintenance remains elusive. This randomized trial examined whether learning a novel set of "stability skills" before losing weight improved long-term weight management. Stability skills were designed to optimize individuals' current satisfaction…

  7. A double-blind randomized control trial of diazepam

    PubMed Central

    1983-01-01

    A double-blind randomized controlled trial of diazepam against placebo in the management of minor conditions seen in general practice demonstrated that administration of either diazepam or placebo was associated with a substantial reduction in symptomatology three weeks later. There was no demonstrable difference between diazepam and placebo. PMID:6358487

  8. Using Randomized Controlled Trials to Evaluate Interventions for Releasing Prisoners

    ERIC Educational Resources Information Center

    Pettus-Davis, Carrie; Howard, Matthew Owen; Dunnigan, Allison; Scheyett, Anna M.; Roberts-Lewis, Amelia

    2016-01-01

    Randomized controlled trials (RCTs) are rarely used to evaluate social and behavioral interventions designed for releasing prisoners. Objective: We use a pilot RCT of a social support intervention (Support Matters) as a case example to discuss obstacles and strategies for conducting RCT intervention evaluations that span prison and community…

  9. Intra-cluster correlation selection for cluster randomized trials.

    PubMed

    Westgate, Philip M

    2016-08-30

    In this paper, we give focus to cluster randomized trials, also known as group randomized trials, which randomize clusters, or groups, of subjects to different trial arms, such as intervention or control. Outcomes from subjects within the same cluster tend to exhibit an exchangeable correlation measured by the intra-cluster correlation coefficient (ICC). Our primary interest is to test if the intervention has an impact on the marginal mean of an outcome. Using recently developed methods, we propose how to select a working ICC structure with the goal of choosing the structure that results in the smallest standard errors for regression parameter estimates and thus the greatest power for this test. Specifically, we utilize small-sample corrections for the estimation of the covariance matrix of regression parameter estimates. This matrix is incorporated within correlation selection criteria proposed in the generalized estimating equations literature to choose one of multiple working ICC structures under consideration. We demonstrate the potential power and utility of this approach when used in cluster randomized trial settings via a simulation study and application example, and we discuss practical considerations for its use in practice. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26924419

  10. Randomized Trial of Drug Abuse Treatment-Linkage Strategies

    ERIC Educational Resources Information Center

    Sorenson, James L.; Masson, Carmen L.; Delucchi, Kevin; Sporer, Karl; Barnett, Paul G.; Mitsuishi, Fumi; Lin, Christine; Song, Yong; Chen, TeChieh; Hall, Sharon M.

    2005-01-01

    A clinical trial contrasted 2 interventions designed to link opioid-dependent hospital patients to drug abuse treatment. The 126 out-of-treatment participants were randomly assigned to (a) case management, (b) voucher for free methadone maintenance treatment (MMT), (c) case management plus voucher, or (d) usual care. Services were provided for 6…

  11. Teacher Awareness Program on Child Abuse: A Randomized Controlled Trial.

    ERIC Educational Resources Information Center

    McGrath, Patrick; And Others

    1987-01-01

    Because teachers lack knowledge of the law, of school board policies, and of issues regarding child abuse and neglect, a professional development workshop was developed and presented to all teachers in the Ottawa Public Schools. Evaluation by a randomized controlled trial showed the workshop effective in increasing and maintaining knowledge.…

  12. A Randomized Trial of Text2Quit

    PubMed Central

    Abroms, Lorien C.; Boal, Ashley L.; Simmens, Samuel J.; Mendel, Judith A.; Windsor, Richard A.

    2014-01-01

    Background Text messaging programs on mobile phones have shown some promise in helping people quit smoking. Text2Quit is an automated, personalized, interactive mobile health program that sends text messages to offer advice, support, and reminders about quitting smoking. Purpose To evaluate the effect of Text2Quit on biochemically confirmed repeated point prevalence abstinence in the context of an RCT conducted in the U.S. Methods Participants (n=503) were recruited on the Internet and randomized to receive Text2Quit or self-help material. Between 2011 and 2013, participants were surveyed at baseline and at 1, 3, and 6 months post-enrollment to assess smoking status. Saliva was collected from participants who reported not smoking in the past 7 days at the 6-month follow-up. An intent to treat analysis was used, and those lost to follow-up were categorized as smokers. All analyses were completed in 2013. Results Biochemically confirmed repeated point prevalence abstinence favored the intervention group, with 11.1% abstinent compared to 5.0% of the control group (relative risk [RR]=2.22, CI=1.16, 4.26, p<0.05). Similarly, self reported repeated point prevalence abstinence was higher in the intervention group (19.9%) than in the control group (10.0%) (p<0.01). Effects were found to be uniform across the analyzed demographic subgroups, although suggestive of a larger effect for non-whites than whites. Conclusions These results provide initial support for the relative efficacy of the Text2Quit program. PMID:24913220

  13. Valerian for insomnia: a systematic review of randomized clinical trials.

    PubMed

    Stevinson; Ernst

    2000-04-01

    Objective: To systematically review the evidence for the effects of the herb valerian (Valeriana officinalis) on insomnia, based on randomized, placebo-controlled, double-blind trials.Background: Valerian has long been advocated and used for promoting sleep but until quite recently evidence was solely anecdotal. However, during the last two decades a number of clinical trials have been conducted.Materials and methods: Systematic literature searches were performed to locate randomized, placebo-controlled, double-blind trials measuring the effect of valerian monopreparations on sleep in human participants. Data were extracted in a standardized manner and methodological quality was assessed by the Jadad score.Results: Nine trials were located meeting the selection criteria. The findings of the studies were contradictory and there was great inconsistency between trials in terms of patients, experimental design and procedures and methodological quality.Conclusion: The evidence for valerian as a treatment for insomnia is inconclusive. There is a need for rigorous trials to determine its efficacy. PMID:10767649

  14. Methods for analyzing cost effectiveness data from cluster randomized trials

    PubMed Central

    Bachmann, Max O; Fairall, Lara; Clark, Allan; Mugford, Miranda

    2007-01-01

    Background Measurement of individuals' costs and outcomes in randomized trials allows uncertainty about cost effectiveness to be quantified. Uncertainty is expressed as probabilities that an intervention is cost effective, and confidence intervals of incremental cost effectiveness ratios. Randomizing clusters instead of individuals tends to increase uncertainty but such data are often analysed incorrectly in published studies. Methods We used data from a cluster randomized trial to demonstrate five appropriate analytic methods: 1) joint modeling of costs and effects with two-stage non-parametric bootstrap sampling of clusters then individuals, 2) joint modeling of costs and effects with Bayesian hierarchical models and 3) linear regression of net benefits at different willingness to pay levels using a) least squares regression with Huber-White robust adjustment of errors, b) a least squares hierarchical model and c) a Bayesian hierarchical model. Results All five methods produced similar results, with greater uncertainty than if cluster randomization was not accounted for. Conclusion Cost effectiveness analyses alongside cluster randomized trials need to account for study design. Several theoretically coherent methods can be implemented with common statistical software. PMID:17822546

  15. Physiologic Responsiveness Should Guide Entry into Randomized Controlled Trials.

    PubMed

    Goligher, Ewan C; Kavanagh, Brian P; Rubenfeld, Gordon D; Ferguson, Niall D

    2015-12-15

    Most randomized trials in critical care report no mortality benefit; this may reflect competing pathogenic mechanisms, patient heterogeneity, or true ineffectiveness of interventions. We hypothesize that in acute respiratory distress syndrome (ARDS), randomizing only those patients who show a favorable physiological response to an intervention would help ensure that only those likely to benefit would be entered into the study. If true, this would decrease study "noise" and reduce required sample size, thereby increasing the chances of finding true-positive outcomes. It would also lessen the chances of exposing patients to treatments that are unlikely to help or that could cause harm. We present a reanalysis of randomized clinical trials of positive end-expiratory pressure in ARDS that support this hypothesis. PMID:25580530

  16. Cost-Effectiveness of a Long-Term Internet-Delivered Worksite Health Promotion Programme on Physical Activity and Nutrition: A Cluster Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Robroek, Suzan J. W.; Polinder, Suzanne; Bredt, Folef J.; Burdorf, Alex

    2012-01-01

    This study aims to evaluate the cost-effectiveness of a long-term workplace health promotion programme on physical activity (PA) and nutrition. In total, 924 participants enrolled in a 2-year cluster randomized controlled trial, with departments (n = 74) within companies (n = 6) as the unit of randomization. The intervention was compared with a…

  17. Central Retinal Enrichment Supplementation Trials (CREST): Design and Methodology of the CREST Randomized Controlled Trials

    PubMed Central

    Beatty, Stephen; Stack, Jim; Dennison, Jessica; O’Regan, Sarah; Meagher, Katherine A.; Peto, Tunde; Nolan, John

    2014-01-01

    Purpose The Central Retinal Enrichment Supplementation Trials (CREST) aim to investigate the potential impact of macular pigment (MP) enrichment, following supplementation with a formulation containing 10 mg lutein (L), 2 mg zeaxanthin (Z) and 10 mg meso-zeaxanthin (MZ), on visual function in normal subjects (Trial 1) and in subjects with early age-related macular degeneration (AMD; Trial 2). Methods CREST is a single center, double-blind, randomized clinical trial. Trial 1 (12-month follow-up) subjects are randomly assigned to a formulation containing 10 mg L, 10 mg MZ and 2 mg Z (n = 60) or placebo (n = 60). Trial 2 (24-month follow-up) subjects are randomly assigned to a formulation containing 10 mg L, 10 mg MZ, 2 mg Z plus 500 mg vitamin C, 400 IU vitamin E, 25 mg zinc and 2 mg copper (Intervention A; n = 75) or 10 mg L and 2 mg Z plus 500 mg vitamin C, 400 IU vitamin E, 25 mg zinc and 2 mg copper (Intervention B; n = 75). Contrast sensitivity (CS) at 6 cycles per degree represents the primary outcome measure in each trial. Secondary outcomes include: CS at other spatial frequencies, MP, best-corrected visual acuity, glare disability, photostress recovery, light scatter, cognitive function, foveal architecture, serum carotenoid concentrations, and subjective visual function. For Trial 2, AMD morphology, reading speed and reading acuity are also being recorded. Conclusions CREST is the first study to investigate the impact of supplementation with all three macular carotenoids in the context of a large, double-blind, randomized clinical trial. PMID:24621122

  18. Project Management of Randomized Clinical Trials: A Narrative Review

    PubMed Central

    Goodarzynejad, Hamidreza; Babamahmoodi, Abdolreza

    2015-01-01

    Context: A well-structured protocol for a clinical trial may be able to answer clinical questions, but it cannot be deemed enough to ensure success in the face of incompetent management of time as well as human and economic resources. To address this problem, in this article, we present our literature review on evidence as to how a good knowledge of proper management among researchers can enhance the likelihood of the success of clinical trial projects. Evidence Acquisition: Using multiple search strategies, we conducted a literature review on published studies in the English language from 2002 to 2012 by searching the Cochrane Database of Systematic Reviews, MEDLINE, Google Scholar, and EMBASE. Results: Our review suggests that a successful trial requires a work plan or work scope as well as a timeline. The trial manager should subsequently manage the study in accordance with the plan and the timeline. Many research units have called for a clinical project manager with scientific background and regulatory skills to effect coordination among various aspects of a clinical trial. Conclusions: Project management may benefit both the managerial and scientific aspects of medical projects and reduce fund waste. However, little has been written to date on project management in the context of clinical research. The suggestions represent the views of the individual authors. To provide a high level of evidence in this regard, we recommend that a randomized controlled trial be performed to compare trial projects progressed with and without the use of project management. PMID:26430517

  19. Leveraging prognostic baseline variables to gain precision in randomized trials.

    PubMed

    Colantuoni, Elizabeth; Rosenblum, Michael

    2015-08-15

    We focus on estimating the average treatment effect in a randomized trial. If baseline variables are correlated with the outcome, then appropriately adjusting for these variables can improve precision. An example is the analysis of covariance (ANCOVA) estimator, which applies when the outcome is continuous, the quantity of interest is the difference in mean outcomes comparing treatment versus control, and a linear model with only main effects is used. ANCOVA is guaranteed to be at least as precise as the standard unadjusted estimator, asymptotically, under no parametric model assumptions and also is locally semiparametric efficient. Recently, several estimators have been developed that extend these desirable properties to more general settings that allow any real-valued outcome (e.g., binary or count), contrasts other than the difference in mean outcomes (such as the relative risk), and estimators based on a large class of generalized linear models (including logistic regression). To the best of our knowledge, we give the first simulation study in the context of randomized trials that compares these estimators. Furthermore, our simulations are not based on parametric models; instead, our simulations are based on resampling data from completed randomized trials in stroke and HIV in order to assess estimator performance in realistic scenarios. We provide practical guidance on when these estimators are likely to provide substantial precision gains and describe a quick assessment method that allows clinical investigators to determine whether these estimators could be useful in their specific trial contexts. PMID:25872751

  20. Leveraging prognostic baseline variables to gain precision in randomized trials

    PubMed Central

    Colantuoni, Elizabeth; Rosenblum, Michael

    2015-01-01

    We focus on estimating the average treatment effect in a randomized trial. If baseline variables are correlated with the outcome, then appropriately adjusting for these variables can improve precision. An example is the analysis of covariance (ANCOVA) estimator, which applies when the outcome is continuous, the quantity of interest is the difference in mean outcomes comparing treatment versus control, and a linear model with only main effects is used. ANCOVA is guaranteed to be at least as precise as the standard unadjusted estimator, asymptotically, under no parametric model assumptions and also is locally semiparametric efficient. Recently, several estimators have been developed that extend these desirable properties to more general settings that allow any real-valued outcome (e.g., binary or count), contrasts other than the difference in mean outcomes (such as the relative risk), and estimators based on a large class of generalized linear models (including logistic regression). To the best of our knowledge, we give the first simulation study in the context of randomized trials that compares these estimators. Furthermore, our simulations are not based on parametric models; instead, our simulations are based on resampling data from completed randomized trials in stroke and HIV in order to assess estimator performance in realistic scenarios. We provide practical guidance on when these estimators are likely to provide substantial precision gains and describe a quick assessment method that allows clinical investigators to determine whether these estimators could be useful in their specific trial contexts. PMID:25872751

  1. Experiences of a long-term randomized controlled prevention trial in a maiden environment: Estonian Postmenopausal Hormone Therapy trial

    PubMed Central

    Hovi, Sirpa-Liisa; Veerus, Piret; Rahu, Mati; Hemminki, Elina

    2008-01-01

    Background Preventive drugs require long-term trials to show their effectiveness or harms and often a lot of changes occur during post-marketing studies. The purpose of this article is to describe the research process in a long-term randomized controlled trial and discuss the impact and consequences of changes in the research environment. Methods The Estonian Postmenopausal Hormone Therapy trial (EPHT), originally planned to continue for five years, was planned in co-operation with the Women's International Study of Long-Duration Oestrogen after Menopause (WISDOM) in the UK. In addition to health outcomes, EPHT was specifically designed to study the impact of postmenopausal hormone therapy (HT) on health services utilization. Results After EPHT recruited in 1999–2001 the Women's Health Initiative (WHI) in the USA decided to stop the estrogen-progestin trial after a mean of 5.2 years in July 2002 because of increased risk of breast cancer and later in 2004 the estrogen-only trial because HT increased the risk of stroke, decreased the risk of hip fracture, and did not affect coronary heart disease incidence. WISDOM was halted in autumn 2002. These decisions had a major influence on EPHT. Conclusion Changes in Estonian society challenged EPHT to find a balance between the needs of achieving responses to the trial aims with a limited budget and simultaneously maintaining the safety of trial participants. Flexibility was the main key for success. Rapid changes are not limited only to transiting societies but are true also in developed countries and the risk must be included in planning all long-term trials. The role of ethical and data monitoring committees in situations with emerging new data from other studies needs specification. Longer funding for preventive trials and more flexibility in budgeting are mandatory. Who should prove the effectiveness of an (old) drug for a new preventive indication? In preventive drug trials companies may donate drugs but they take a

  2. Randomized Controlled Trials of Add-On Antidepressants in Schizophrenia

    PubMed Central

    Joffe, Grigori; Stenberg, Jan-Henry

    2015-01-01

    Background: Despite adequate treatment with antipsychotics, a substantial number of patients with schizophrenia demonstrate only suboptimal clinical outcome. To overcome this challenge, various psychopharmacological combination strategies have been used, including antidepressants added to antipsychotics. Methods: To analyze the efficacy of add-on antidepressants for the treatment of negative, positive, cognitive, depressive, and antipsychotic-induced extrapyramidal symptoms in schizophrenia, published randomized controlled trials assessing the efficacy of adjunctive antidepressants in schizophrenia were reviewed using the following parameters: baseline clinical characteristics and number of patients, their on-going antipsychotic treatment, dosage of the add-on antidepressants, duration of the trial, efficacy measures, and outcomes. Results: There were 36 randomized controlled trials reported in 41 journal publications (n=1582). The antidepressants used were the selective serotonin reuptake inhibitors, duloxetine, imipramine, mianserin, mirtazapine, nefazodone, reboxetin, trazodone, and bupropion. Mirtazapine and mianserin showed somewhat consistent efficacy for negative symptoms and both seemed to enhance neurocognition. Trazodone and nefazodone appeared to improve the antipsychotics-induced extrapyramidal symptoms. Imipramine and duloxetine tended to improve depressive symptoms. No clear evidence supporting selective serotonin reuptake inhibitors’ efficacy on any clinical domain of schizophrenia was found. Add-on antidepressants did not worsen psychosis. Conclusions: Despite a substantial number of randomized controlled trials, the overall efficacy of add-on antidepressants in schizophrenia remains uncertain mainly due to methodological issues. Some differences in efficacy on several schizophrenia domains seem, however, to exist and to vary by the antidepressant subgroups—plausibly due to differences in the mechanisms of action. Antidepressants may not worsen

  3. Mediterranean dietary pattern and depression: the PREDIMED randomized trial

    PubMed Central

    2013-01-01

    Background A few observational studies have found an inverse association between adherence to a Mediterranean diet and the risk of depression. Randomized trials with an intervention based on this dietary pattern could provide the most definitive answer to the findings reported by observational studies. The aim of this study was to compare in a randomized trial the effects of two Mediterranean diets versus a low-fat diet on depression risk after at least 3 years of intervention. Methods This was a multicenter, randomized, primary prevention field trial of cardiovascular disease (Prevención con Dieta Mediterránea (PREDIMED Study)) based on community-dwelling men aged 55 to 80 years and women aged 60 to 80 years at high risk of cardiovascular disease (51% of them had type 2 diabetes; DM2) attending primary care centers affiliated with 11 Spanish teaching hospitals. Primary analyses were performed on an intention-to-treat basis. Cox regression models were used to assess the relationship between the nutritional intervention groups and the incidence of depression. Results We identified 224 new cases of depression during follow-up. There was an inverse association with depression for participants assigned to a Mediterranean diet supplemented with nuts (multivariate hazard ratio (HR) 0.78; 95% confidence interval (CI) 0.55 to 1.10) compared with participants assigned to the control group, although this was not significant. However, when the analysis was restricted to participants with DM2, the magnitude of the effect of the intervention with the Mediterranean diet supplemented with nuts did reach statistical significance (multivariate HR = 0.59; 95% CI 0.36 to 0.98). Conclusions The result suggest that a Mediterranean diet supplemented with nuts could exert a beneficial effect on the risk of depression in patients with DM2. Trial registration This trial has been registered in the Current Controlled Trials with the number ISRCTN 35739639 PMID:24229349

  4. Analyzing Direct Effects in Randomized Trials with Secondary Interventions: An Application to HIV Prevention Trials.

    PubMed

    Rosenblum, Michael; Jewell, Nicholas P; van der Laan, Mark; Shiboski, Steve; van der Straten, Ariane; Padian, Nancy

    2009-04-01

    The Methods for Improving Reproductive Health in Africa (MIRA) trial is a recently completed randomized trial that investigated the effect of diaphragm and lubricant gel use in reducing HIV infection among susceptible women. 5,045 women were randomly assigned to either the active treatment arm or not. Additionally, all subjects in both arms received intensive condom counselling and provision, the "gold standard" HIV prevention barrier method. There was much lower reported condom use in the intervention arm than in the control arm, making it difficult to answer important public health questions based solely on the intention-to-treat analysis. We adapt an analysis technique from causal inference to estimate the "direct effects" of assignment to the diaphragm arm, adjusting for condom use in an appropriate sense. Issues raised in the MIRA trial apply to other trials of HIV prevention methods, some of which are currently being conducted or designed. PMID:20827388

  5. Analyzing Direct Effects in Randomized Trials with Secondary Interventions: An Application to HIV Prevention Trials

    PubMed Central

    Rosenblum, Michael; Jewell, Nicholas P.; van der Laan, Mark; Shiboski, Steve; van der Straten, Ariane; Padian, Nancy

    2010-01-01

    Summary The Methods for Improving Reproductive Health in Africa (MIRA) trial is a recently completed randomized trial that investigated the effect of diaphragm and lubricant gel use in reducing HIV infection among susceptible women. 5,045 women were randomly assigned to either the active treatment arm or not. Additionally, all subjects in both arms received intensive condom counselling and provision, the “gold standard” HIV prevention barrier method. There was much lower reported condom use in the intervention arm than in the control arm, making it difficult to answer important public health questions based solely on the intention-to-treat analysis. We adapt an analysis technique from causal inference to estimate the “direct effects” of assignment to the diaphragm arm, adjusting for condom use in an appropriate sense. Issues raised in the MIRA trial apply to other trials of HIV prevention methods, some of which are currently being conducted or designed. PMID:20827388

  6. Using Big Data to Emulate a Target Trial When a Randomized Trial Is Not Available.

    PubMed

    Hernán, Miguel A; Robins, James M

    2016-04-15

    Ideally, questions about comparative effectiveness or safety would be answered using an appropriately designed and conducted randomized experiment. When we cannot conduct a randomized experiment, we analyze observational data. Causal inference from large observational databases (big data) can be viewed as an attempt to emulate a randomized experiment-the target experiment or target trial-that would answer the question of interest. When the goal is to guide decisions among several strategies, causal analyses of observational data need to be evaluated with respect to how well they emulate a particular target trial. We outline a framework for comparative effectiveness research using big data that makes the target trial explicit. This framework channels counterfactual theory for comparing the effects of sustained treatment strategies, organizes analytic approaches, provides a structured process for the criticism of observational studies, and helps avoid common methodologic pitfalls. PMID:26994063

  7. Preference in Random Assignment: Implications for the Interpretation of Randomized Trials

    PubMed Central

    Gold, Paul B.; Hargreaves, William A.; Aronson, Elliot; Bickman, Leonard; Barreira, Paul J.; Jones, Danson R.; Rodican, Charles F.; Fisher, William H.

    2009-01-01

    Random assignment to a preferred experimental condition can increase service engagement and enhance outcomes, while assignment to a less-preferred condition can discourage service receipt and limit outcome attainment. We examined randomized trials for one prominent psychiatric rehabilitation intervention, supported employment, to gauge how often assignment preference might have complicated the interpretation of findings. Condition descriptions, and greater early attrition from services-as-usual comparison conditions, suggest that many study enrollees favored assignment to new rapid-job-placement supported employment, but no study took this possibility into account. Reviews of trials in other service fields are needed to determine whether this design problem is widespread. PMID:19434489

  8. Internet-based randomized controlled trials: a systematic review

    PubMed Central

    Mathieu, Erin; McGeechan, Kevin; Barratt, Alexandra; Herbert, Robert

    2013-01-01

    Background The internet is increasingly being used to conduct randomized controlled trials (RCTs). Knowledge of the types of interventions evaluated and the methodological quality of these trials could inform decisions about whether to conduct future trials using conventional methods, fully online or a mixture of the two. Objective To identify and describe the scope of internet-based RCTs for human health condition interventions and evaluate their methodological quality. Methods A systematic review of RCTs of any health intervention conducted fully or primarily on the internet was carried out. Results 23 fully and 27 primarily internet-based RCTs were identified. The first was conducted in 2000. The majority of trials evaluated interventions that involved providing health information to participants, but a few evaluated self-administered interventions (eg, valerian, stretching). Methodological quality was variable and the methods were generally poorly reported. The risk of bias was low in only a small number of trials; most had substantial methodological shortcomings. Only one trial was identified as meeting all criteria for adequate methodological quality. A particular problem was high rates of loss to follow-up (fully online: mean 47%; primarily online: mean 36%). Conclusions It is theoretically possible but perhaps difficult to test the effectiveness of health interventions rigorously with RCTs conducted fully or primarily over the internet. The use of the internet to conduct trials is more suited to pragmatic rather than explanatory trials. The main limitation of these trials is that they typically experience high rates of loss to follow-up. Methodological standards now accepted for traditional RCTs needs to be evident for online RCTs as well, especially in reporting of their methods. PMID:23065196

  9. Results, rhetoric, and randomized trials: the case of donepezil.

    PubMed

    Gilstad, John R; Finucane, Thomas E

    2008-08-01

    Whether donepezil provides meaningful benefit to patients with Alzheimer's disease (AD) is controversial, but drug sales annually total billions of dollars. A review of data from published randomized clinical trials (RCTs) found rhetorical patterns that may encourage use of this drug. To create a reproducible observation, the sentences occurring at five specific text sites in all 18 RCTs of donepezil for AD were tabulated, as were study design, sources of financial support, and outcomes that could be compared between trials. Rhetoric in the 13 vendor-supported trials (15 publications) was strongly positive. Three early trials used the motif "efficacious (or effective) ... treating ... symptoms" four times. "Well-tolerated and efficacious" or an equivalent motif appeared 11 times in five RCTs. Nine RCTs referred 15 times to previously proven effectiveness. Seven trials encourage off-label use, for "early" cognitive impairment, severe dementia in advance of the Food and Drug Administration labeling change, or behavioral symptoms. These rhetorical motifs and themes appeared only in the vendor-supported trials. Trials without vendor support described the drug's effects as "small" or absent; two emphasized the need for better treatments. RCT results were highly consistent in all trials; the small differences do not explain differences in rhetoric. At these text sites in the primary research literature on donepezil for AD, uniformly positive rhetoric is present in all vendor-supported RCTs. Reference to the limited benefit of donepezil is confined to RCTs without vendor support. Data in the trials are highly consistent. This observation generates the hypothesis that rhetoric in vendor-supported published RCTs may promote vendors' products. PMID:18662199

  10. Complementary feeding: a Global Network cluster randomized controlled trial

    PubMed Central

    2011-01-01

    Background Inadequate and inappropriate complementary feeding are major factors contributing to excess morbidity and mortality in young children in low resource settings. Animal source foods in particular are cited as essential to achieve micronutrient requirements. The efficacy of the recommendation for regular meat consumption, however, has not been systematically evaluated. Methods/Design A cluster randomized efficacy trial was designed to test the hypothesis that 12 months of daily intake of beef added as a complementary food would result in greater linear growth velocity than a micronutrient fortified equi-caloric rice-soy cereal supplement. The study is being conducted in 4 sites of the Global Network for Women's and Children's Health Research located in Guatemala, Pakistan, Democratic Republic of the Congo (DRC) and Zambia in communities with toddler stunting rates of at least 20%. Five clusters per country were randomized to each of the food arms, with 30 infants in each cluster. The daily meat or cereal supplement was delivered to the home by community coordinators, starting when the infants were 6 months of age and continuing through 18 months. All participating mothers received nutrition education messages to enhance complementary feeding practices delivered by study coordinators and through posters at the local health center. Outcome measures, obtained at 6, 9, 12, and 18 months by a separate assessment team, included anthropometry; dietary variety and diversity scores; biomarkers of iron, zinc and Vitamin B12 status (18 months); neurocognitive development (12 and 18 months); and incidence of infectious morbidity throughout the trial. The trial was supervised by a trial steering committee, and an independent data monitoring committee provided oversight for the safety and conduct of the trial. Discussion Findings from this trial will test the efficacy of daily intake of meat commencing at age 6 months and, if beneficial, will provide a strong rationale

  11. Randomized controlled trials – a matter of design

    PubMed Central

    Spieth, Peter Markus; Kubasch, Anne Sophie; Penzlin, Ana Isabel; Illigens, Ben Min-Woo; Barlinn, Kristian; Siepmann, Timo

    2016-01-01

    Randomized controlled trials (RCTs) are the hallmark of evidence-based medicine and form the basis for translating research data into clinical practice. This review summarizes commonly applied designs and quality indicators of RCTs to provide guidance in interpreting and critically evaluating clinical research data. It further reflects on the principle of equipoise and its practical applicability to clinical science with an emphasis on critical care and neurological research. We performed a review of educational material, review articles, methodological studies, and published clinical trials using the databases MEDLINE, PubMed, and ClinicalTrials.gov. The most relevant recommendations regarding design, conduction, and reporting of RCTs may include the following: 1) clinically relevant end points should be defined a priori, and an unbiased analysis and report of the study results should be warranted, 2) both significant and nonsignificant results should be objectively reported and published, 3) structured study design and performance as indicated in the Consolidated Standards of Reporting Trials statement should be employed as well as registration in a public trial database, 4) potential conflicts of interest and funding sources should be disclaimed in study report or publication, and 5) in the comparison of experimental treatment with standard care, preplanned interim analyses during an ongoing RCT can aid in maintaining clinical equipoise by assessing benefit, harm, or futility, thus allowing decision on continuation or termination of the trial. PMID:27354804

  12. Preconception maternal nutrition: a multi-site randomized controlled trial

    PubMed Central

    2014-01-01

    Background Research directed to optimizing maternal nutrition commencing prior to conception remains very limited, despite suggestive evidence of its importance in addition to ensuring an optimal nutrition environment in the periconceptional period and throughout the first trimester of pregnancy. Methods/Study design This is an individually randomized controlled trial of the impact on birth length (primary outcome) of the time at which a maternal nutrition intervention is commenced: Arm 1: ≥ 3 mo preconception vs. Arm 2: 12-14 wk gestation vs. Arm 3: none. 192 (derived from 480) randomized mothers and living offspring in each arm in each of four research sites (Guatemala, India, Pakistan, Democratic Republic of the Congo). The intervention is a daily 20 g lipid-based (118 kcal) multi-micronutient (MMN) supplement. Women randomized to receive this intervention with body mass index (BMI) <20 or whose gestational weight gain is low will receive an additional 300 kcal/d as a balanced energy-protein supplement. Researchers will visit homes biweekly to deliver intervention and monitor compliance, pregnancy status and morbidity; ensure prenatal and delivery care; and promote breast feeding. The primary outcome is birth length. Secondary outcomes include: fetal length at 12 and 34 wk; incidence of low birth weight (LBW); neonatal/infant anthropometry 0-6 mo of age; infectious disease morbidity; maternal, fetal, newborn, and infant epigenetics; maternal and infant nutritional status; maternal and infant microbiome; gut inflammatory biomarkers and bioactive and nutritive compounds in breast milk. The primary analysis will compare birth Length-for-Age Z-score (LAZ) among trial arms (independently for each site, estimated effect size: 0.35). Additional statistical analyses will examine the secondary outcomes and a pooled analysis of data from all sites. Discussion Positive results of this trial will support a paradigm shift in attention to nutrition of all females of

  13. Participant Informed Consent in Cluster Randomized Trials: Review

    PubMed Central

    Giraudeau, Bruno; Caille, Agnès; Le Gouge, Amélie; Ravaud, Philippe

    2012-01-01

    Background The Nuremberg code defines the general ethical framework of medical research with participant consent as its cornerstone. In cluster randomized trials (CRT), obtaining participant informed consent raises logistic and methodologic concerns. First, with randomization of large clusters such as geographical areas, obtaining individual informed consent may be impossible. Second, participants in randomized clusters cannot avoid certain interventions, which implies that participant informed consent refers only to data collection, not administration of an intervention. Third, complete participant information may be a source of selection bias, which then raises methodological concerns. We assessed whether participant informed consent was required in such trials, which type of consent was required, and whether the trial was at risk of selection bias because of the very nature of participant information. Methods and Findings We systematically reviewed all reports of CRT published in MEDLINE in 2008 and surveyed corresponding authors regarding the nature of the informed consent and the process of participant inclusion. We identified 173 reports and obtained an answer from 113 authors (65.3%). In total, 23.7% of the reports lacked information on ethics committee approval or participant consent, 53.1% of authors declared that participant consent was for data collection only and 58.5% that the group allocation was not specified for participants. The process of recruitment (chronology of participant recruitment with regard to cluster randomization) was rarely reported, and we estimated that only 56.6% of the trials were free of potential selection bias. Conclusions For CRTs, the reporting of ethics committee approval and participant informed consent is less than optimal. Reports should describe whether participants consented for administration of an intervention and/or data collection. Finally, the process of participant recruitment should be fully described (namely

  14. Teacher awareness program on child abuse: a randomized controlled trial.

    PubMed

    McGrath, P; Cappelli, M; Wiseman, D; Khalil, N; Allan, B

    1987-01-01

    Teachers have a significant role in preventing, detecting and reporting child abuse and neglect. They are hindered in fulfilling this role by a serious lack of knowledge of the law, of school board policies, and of maltreatment. A comprehensive professional development workshop was developed and presented to elementary school teachers. The package was evaluated by means of a randomized controlled trial. The workshop proved to be effective in increasing and maintaining knowledge. PMID:3828866

  15. Use of group-randomized trials in pet population research.

    PubMed

    Lord, L K; Wittum, T E; Scarlett, J M

    2007-12-14

    Communities invest considerable resources to address the animal welfare and public health concerns resulting from unwanted pet animals. Traditionally, research in this area has enumerated the pet-owning population, described pet population dynamics in individual communities, and estimated national euthanasia figures. Recent research has investigated the human-animal bond and explored the community implications of managed feral cat colonies. These reports have utilized traditional epidemiologic study designs to generate observational data to describe populations and measure associations. However, rigorous scientific evaluations of potential interventions at the group level have been lacking. Group-randomized trials have been used extensively in public health research to evaluate interventions that change a population's behavior, not just the behavior of selected individuals. We briefly describe the strengths and limitations of group-randomized trials as they are used to evaluate interventions that promote social and behavioral changes in the human public health field. We extend these examples to suggest the appropriate application of group-randomized trials for pet population dynamics research. PMID:17707934

  16. Repeated randomization and matching in multi-arm trials.

    PubMed

    Xu, Zhenzhen; Kalbfleisch, John D

    2013-12-01

    Cluster randomized trials with relatively few clusters have been widely used in recent years for evaluation of health-care strategies. The balance match weighted (BMW) design, introduced in Xu and Kalbfleisch (2010, Biometrics 66, 813-823), applies the optimal full matching with constraints technique to a prospective randomized design with the aim of minimizing the mean squared error (MSE) of the treatment effect estimator. This is accomplished through consideration of M independent randomizations of the experimental units and then selecting the one which provides the most balance evaluated by matching on the estimated propensity scores. Often in practice, clinical trials may involve more than two treatment arms and multiple treatment options need to be evaluated. Therefore, we consider extensions of the BMW propensity score matching method to allow for studies with three or more arms. In this article, we propose three approaches to extend the BMW design to clinical trials with more than two arms and evaluate the property of the extended design in simulation studies. PMID:24134592

  17. Cardiovascular Effects of Dietary Salt Intake in Aged Healthy Cats: A 2-Year Prospective Randomized, Blinded, and Controlled Study

    PubMed Central

    Chetboul, Valérie; Reynolds, Brice Stéphane; Trehiou-Sechi, Emilie; Nguyen, Patrick; Concordet, Didier; Sampedrano, Carolina Carlos; Testault, Isabelle; Elliott, Jonathan; Abadie, Jérôme; Biourge, Vincent; Lefebvre, Hervé Pierre

    2014-01-01

    High salt dry expanded diets are commercially available for cats to increase water intake and urine volume, as part of the prevention or treatment of naturally occurring urinary stone formation (calcium oxalates and struvites). However, chronic high salt intake may have potential cardiovascular adverse effects in both humans, especially in aging individuals, and several animal models. The objective of this prospective, randomized, blinded, and controlled study was to assess the long-term cardiovascular effects of high salt intake in healthy aged cats. Twenty healthy neutered cats (10.1±2.4 years) were randomly allocated into 2 matched groups. One group was fed a high salt diet (3.1 g/Mcal sodium, 5.5 g/Mcal chloride) and the other group a control diet of same composition except for salt content (1.0 g/Mcal sodium, 2.2 g/Mcal chloride). Clinical examination, systolic and diastolic arterial blood pressure measurements, standard transthoracic echocardiography and conventional Doppler examinations were repeatedly performed on non-sedated cats by trained observers before and over 24 months after diet implementation. Radial and longitudinal velocities of the left ventricular free wall and the interventricular septum were also assessed in systole and diastole using 2-dimensional color tissue Doppler imaging. Statistics were performed using a general linear model. No significant effect of dietary salt intake was observed on systolic and diastolic arterial blood pressure values. Out of the 33 tested imaging variables, the only one affected by dietary salt intake was the radial early on late diastolic velocity ratio assessed in the endocardium of the left ventricular free wall, statistically lower in the high salt diet group at 12 months only (P = 0.044). In conclusion, in this study involving healthy aged cats, chronic high dietary salt intake was not associated with an increased risk of systemic arterial hypertension and myocardial dysfunction, as observed in some

  18. The quality of randomized controlled trials in major anesthesiology journals.

    PubMed

    Greenfield, Mary Lou V H; Rosenberg, Andrew L; O'Reilly, Michael; Shanks, Amy M; Sliwinski, Michelle J; Nauss, Michael D

    2005-06-01

    Increased attention has been directed at the quality of randomized controlled trials (RCTs) and how they are being reported. We examined leading anesthesiology journals to identify if there were specific areas for improvement in the design and analysis of published clinical studies. All RCTs that appeared between January 2000 and December 2000 in leading anesthesiology journals (Anesthesiology,Anesthesia & Analgesia,Anaesthesia, and Canadian Journal of Anaesthesia) were retrieved by a MEDLINE search. We used a previously validated assessment tool, including 14 items associated with study quality, to determine a quality score for each article. The overall mean weighted quality score was 44% +/- 16%. Overall average scores were relatively high for appropriate controls (77% +/- 7%) and discussions of side effects (67% +/- 6%). Scores were very low for randomization blinding (5% +/- 2%), blinding observers to results (1% +/- 1%), and post-beta estimates (16% +/- 13%). Important pretreatment clinical predictors were absent in 32% of all studies. Significant improvement in the reporting and conduct of RCTs is required and should focus on randomization methodology, the blinding of investigators, and sample size estimates. Repeat assessments of the literature may improve the adoption of guidelines for the improvement of the quality of randomized controlled trials. PMID:15920210

  19. The HONEYPOT Randomized Controlled Trial Statistical Analysis Plan

    PubMed Central

    Pascoe, Elaine Mary; Lo, Serigne; Scaria, Anish; Badve, Sunil V.; Beller, Elaine Mary; Cass, Alan; Hawley, Carmel Mary; Johnson, David W.

    2013-01-01

    ♦ Background: The HONEYPOT study is a multicenter, open-label, blinded-outcome, randomized controlled trial designed to determine whether, compared with standard topical application of mupirocin for nasal staphylococcal carriage, exit-site application of antibacterial honey reduces the rate of catheter-associated infections in peritoneal dialysis patients. ♦ Objective: To make public the pre-specified statistical analysis principles to be adhered to and the procedures to be performed by statisticians who will analyze the data for the HONEYPOT trial. ♦ Methods: Statisticians and clinical investigators who were blinded to treatment allocation and treatment-related study results and who will remain blinded until the central database is locked for final data extraction and analysis determined the statistical methods and procedures to be used for analysis and wrote the statistical analysis plan. The plan describes basic analysis principles, methods for dealing with a range of commonly encountered data analysis issues, and the specific statistical procedures for analyzing the primary, secondary, and safety outcomes. ♦ Results: A statistical analysis plan containing the pre-specified principles, methods, and procedures to be adhered to in the analysis of the data from the HONEYPOT trial was developed in accordance with international guidelines. The structure and content of the plan provide sufficient detail to meet the guidelines on statistical principles for clinical trials produced by the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use. ♦ Conclusions: Making public the pre-specified statistical analysis plan for the HONEYPOT trial minimizes the potential for bias in the analysis of trial data and the interpretation and reporting of trial results. PMID:23843589

  20. ADAPTIVE MATCHING IN RANDOMIZED TRIALS AND OBSERVATIONAL STUDIES

    PubMed Central

    van der Laan, Mark J.; Balzer, Laura B.; Petersen, Maya L.

    2014-01-01

    SUMMARY In many randomized and observational studies the allocation of treatment among a sample of n independent and identically distributed units is a function of the covariates of all sampled units. As a result, the treatment labels among the units are possibly dependent, complicating estimation and posing challenges for statistical inference. For example, cluster randomized trials frequently sample communities from some target population, construct matched pairs of communities from those included in the sample based on some metric of similarity in baseline community characteristics, and then randomly allocate a treatment and a control intervention within each matched pair. In this case, the observed data can neither be represented as the realization of n independent random variables, nor, contrary to current practice, as the realization of n/2 independent random variables (treating the matched pair as the independent sampling unit). In this paper we study estimation of the average causal effect of a treatment under experimental designs in which treatment allocation potentially depends on the pre-intervention covariates of all units included in the sample. We define efficient targeted minimum loss based estimators for this general design, present a theorem that establishes the desired asymptotic normality of these estimators and allows for asymptotically valid statistical inference, and discuss implementation of these estimators. We further investigate the relative asymptotic efficiency of this design compared with a design in which unit-specific treatment assignment depends only on the units’ covariates. Our findings have practical implications for the optimal design and analysis of pair matched cluster randomized trials, as well as for observational studies in which treatment decisions may depend on characteristics of the entire sample. PMID:25097298

  1. Standards of Reporting of Randomized Controlled Trials in General Surgery

    PubMed Central

    Balasubramanian, Sabapathy P.; Wiener, Martin; Alshameeri, Zeiad; Tiruvoipati, Ravindranath; Elbourne, Diana; Reed, Malcolm W.

    2006-01-01

    Objective: To evaluate the quality of reporting of surgical randomized controlled trials published in surgical and general medical journals using Jadad score, allocation concealment, and adherence to CONSORT guidelines and to identify factors associated with good quality. Summary Background Data: Randomized controlled trials (RCTs) provide the best evidence about the relative effectiveness of different interventions. Improper methodology and reporting of RCTs can lead to erroneous conclusions about treatment effects, which may mislead decision-making in health care at all levels. Methods: Information was obtained on RCTs published in 6 general surgical and 4 general medical journals in the year 2003. The quality of reporting of RCTs was assessed under masked conditions using allocation concealment, Jadad score, and a CONSORT checklist devised for the purpose. Results: Of the 69 RCTs analyzed, only 37.7% had a Jadad score of ≥3, and only 13% of the trials clearly explained allocation concealment. The modified CONSORT score of surgical trials reported in medical journals was significantly higher than those reported in surgical journals (Mann-Whitney U test, P < 0.001). Overall, the modified CONSORT score was higher in studies with higher author numbers (P = 0.03), multicenter studies (P = 0.002), and studies with a declared funding source (P = 0.022). Conclusion: The overall quality of reporting of surgical RCTs was suboptimal. There is a need for improving awareness of the CONSORT statement among authors, reviewers, and editors of surgical journals and better quality control measures for trial reporting and methodology. PMID:17060756

  2. Outcomes in Registered, Ongoing Randomized Controlled Trials of Patient Education

    PubMed Central

    Pino, Cécile; Boutron, Isabelle; Ravaud, Philippe

    2012-01-01

    Background With the increasing prevalence of chronic noncommunicable diseases, patient education is becoming important to strengthen disease prevention and control. We aimed to systematically determine the extent to which registered, ongoing randomized controlled trials (RCTs) evaluated an educational intervention focus on patient-important outcomes (i.e., outcomes measuring patient health status and quality of life). Methods On May 6, 2009, we searched for all ongoing RCTs registered in the World Health Organization International Clinical Trials Registry platform. We used a standardized data extraction form to collect data and determined whether the outcomes assessed were 1) patient-important outcomes such as clinical events, functional status, pain, or quality of life or 2) surrogate outcomes, such as biological outcome, treatment adherence, or patient knowledge. Principal Findings We selected 268 of the 642 potentially eligible studies and assessed a random sample of 150. Patient-important outcomes represented 54% (178 of 333) of all primary outcomes and 46% (286 of 623) of all secondary outcomes. Overall, 69% of trials (104 of 150) used at least one patient-important outcome as a primary outcome and 66% (99 of 150) as a secondary outcome. Finally, for 31% of trials (46 of 150), primary outcomes were only surrogate outcomes. The results varied by medical area. In neuropsychiatric disorders, patient important outcomes represented 84% (51 of 61) of primary outcomes, as compared with 54% (32 of 59) in malignant neoplasm and 18% (4 of 22) in diabetes mellitus trials. In addition, only 35% assessed the long-term impact of interventions (i.e., >6 months). Conclusions There is a need to improve the relevance of outcomes and to assess the long term impact of educational interventions in RCTs. PMID:22916183

  3. Randomized trial of tapas acupressure technique for weight loss maintenance

    PubMed Central

    2012-01-01

    Background Obesity is an urgent public health problem, yet only a few clinical trials have systematically tested the efficacy of long-term weight-loss maintenance interventions. This randomized clinical trial tested the efficacy of a novel mind and body technique for weight-loss maintenance. Methods Participants were obese adults who had completed a six-month behavioral weight-loss program prior to randomization. Those who successfully lost weight were randomized into either an experimental weight-loss maintenance intervention, Tapas Acupressure Technique (TAT®), or a control intervention comprised of social-support group meetings (SS) led by professional facilitators. TAT combines self-applied light pressure to specific acupressure points accompanied by a prescribed sequence of mental steps. Participants in both maintenance conditions attended eight group sessions over six months of active weight loss maintenance intervention, followed by an additional 6 months of no intervention. The main outcome measure was change in weight from the beginning of the weight loss maintenance intervention to 12 months later. Secondary outcomes were change in depression, stress, insomnia, and quality of life. We used analysis of covariance as the primary analysis method. Missing values were replaced using multiple imputation. Results Among 285 randomized participants, 79% were female, mean age was 56 (standard deviation (sd) = 11), mean BMI at randomization was 34 (sd = 5), and mean initial weight loss was 9.8 kg (sd = 5). In the primary outcome model, there was no significant difference in weight regain between the two arms (1.72 kg (se 0.85) weight regain for TAT and 2.96 kg (se 0.96) weight regain for SS, p < 0.097) Tests of between- arm differences for secondary outcomes were also not significant. A secondary analysis showed a significant interaction between treatment and initial weight loss (p < .036), with exploratory post hoc tests showing that greater initial weight loss

  4. Power Calculations for Moderators in Multi-Site Cluster Randomized Trials

    ERIC Educational Resources Information Center

    Spybrook, Jessaca; Kelcey, Ben; Dong, Nianbo

    2016-01-01

    Cluster randomized trials (CRTs), or studies in which intact groups of individuals are randomly assigned to a condition, are becoming more common in evaluation studies of educational programs. A specific type of CRT in which clusters are randomly assigned to treatment within blocks or sites, known as multisite cluster randomized trials (MSCRTs),…

  5. Qigong and fibromyalgia: randomized controlled trials and beyond.

    PubMed

    Sawynok, Jana; Lynch, Mary

    2014-01-01

    Introduction. Qigong is currently considered as meditative movement, mindful exercise, or complementary exercise and is being explored for relief of symptoms in fibromyalgia. Aim. This narrative review summarizes randomized controlled trials, as well as additional studies, of qigong published to the end of 2013 and discusses relevant methodological issues. Results. Controlled trials indicate regular qigong practice (daily, 6-8 weeks) produces improvements in core domains for fibromyalgia (pain, sleep, impact, and physical and mental function) that are maintained at 4-6 months compared to wait-list subjects or baselines. Comparisons with active controls show little difference, but compared to baseline there are significant and comparable effects in both groups. Open-label studies provide information that supports benefit but remain exploratory. An extension trial and case studies involving extended practice (daily, 6-12 months) indicate marked benefits but are limited by the number of participants. Benefit appears to be related to amount of practice. Conclusions. There is considerable potential for qigong to be a useful complementary practice for the management of fibromyalgia. However, there are unique methodological challenges, and exploration of its clinical potential will need to focus on pragmatic issues and consider a spectrum of trial designs. Mechanistic considerations need to consider both system-wide and more specific effects. PMID:25477991

  6. Randomized controlled trials for Alzheimer disease and Parkinson disease.

    PubMed

    Lauretani, Fulvio; Ticinesi, Andrea; Meschi, Tiziana; Teresi, Giulio; Ceda, Gian Paolo; Maggio, Marcello

    2016-01-01

    The continuous increase in elderly and oldest-old population, and subsequent rise in prevalence of chronic neurological diseases like Alzheimer's disease (AD) and Parkinson's disease (PD), are a major challenge for healthcare systems. These two conditions are the most prevalent neurodegenerative diseases in older persons and physicians should engage treatment for these patients. In this field, Randomized Clinical Trials (RCTs) specifically focused on elderly populations are still lacking. The aim of this study was to identify RCTs conducted among AD and PD and to examine the difference between mean age of enrollment and incidence of these two neurodegenerative diseases. We found that the scenario is different between PD and AD. In particular, the enrollment for PD trials seems to include younger persons than AD, although the incidence of both diseases is similar and highest after 80 years old. The consequence of these results could influence conclusive guidelines of treatment in older parkinsonian patients. PMID:27100346

  7. Using baseline data to design a group randomized trial.

    PubMed

    Hughes, James P

    2005-07-15

    Group randomized trials (GRT) are often designed with relatively little preliminary data available to estimate key parameters. In this paper, however, the opposite situation is considered-very good baseline data are available on the primary outcome of interest. These data can then be used to inform key design and analysis decisions such as (i) should the trial be designed as an unmatched or pair-matched study, or stratified in some other fashion; (ii) is analysis of "change from baseline" preferable to using end-of-study data alone; and (iii) what power might be expected by pursuing these various strategies. The results are applied to a GRT for sexually transmitted diseases prevention in Peru. PMID:15779091

  8. Tobacco dependence counseling in a randomized multisite clinical trial.

    PubMed

    Croghan, Ivana T; Trautman, Judith A; Winhusen, Theresa; Ebbert, Jon O; Kropp, Frankie B; Schroeder, Darrell R; Hurt, Richard D

    2012-07-01

    Pharmacotherapy trials for treating tobacco dependence would benefit from behavioral interventions providing treatment consistent with clinical practice guidelines but not directing participants to treatments not evaluated in the trial. The Smoke Free and Living It© behavioral intervention manual includes participant and interventionist guides and is designed to provide both practical counseling and intra-treatment support. We utilized this intervention manual in a multicenter, randomized clinical trial of smokers with attention deficit hyperactivity disorder. In this study, we evaluated how the interventional manual performed in a "train-the-trainer" model requiring uniform counseling across 6 sites and 15 interventionists. We analyzed the skill-adherence of the interventionists and the intervention-adherence of the participants. The 255 randomized participants completed 9.3±2.8 sessions (mean±SD), with 157 participants (61.6%) completing all 11 of the sessions and 221 (86.7%) completing at least 6 of the 11 sessions. Of the 163 sessions for which the study interventionists were evaluated, 156 (95.7%) were rated as adherent to protocol and "meeting expectations" on at least 6 of 7 established criteria, illustrating that fidelity can be maintained with minimal supervision. The self-help and interventionists guides of the Smoke Free and Living It manual can thus be used to provide behavioral intervention with a high rate of adherence by both the interventionists and the participants. This manual meets the requirements of the United States Public Health Service Clinical Practice Guideline, can be adapted to specific research protocols, and provides a useful option for behavioral intervention during clinical trials for smoking cessation. PMID:22406192

  9. Shallow Semantic Parsing of Randomized Controlled Trial Reports

    PubMed Central

    Paek, Hyung; Kogan, Yacov; Thomas, Prem; Codish, Seymour; Krauthammer, Michael

    2006-01-01

    In this work, we are measuring the performance of Propbank-based Machine Learning (ML) for automatically annotating abstracts of Randomized Controlled Trials (RCTs) with semantically meaningful tags. Propbank is a resource of annotated sentences from the Wall Street Journal (WSJ) corpus, and we were interested in assessing performance issues when porting this resource to the medical domain. We compare intra-domain (WSJ/WSJ) with cross-domain (WSJ/medical abstracts) performance. Although the intra-domain performance is superior, we found a reasonable cross-domain performance. PMID:17238412

  10. Neighborhood Effects in a Behavioral Randomized Controlled Trial

    PubMed Central

    Pruitt, Sandi L.; Leonard, Tammy; Murdoch, James; Hughes, Amy; McQueen, Amy; Gupta, Samir

    2015-01-01

    Randomized controlled trials (RCTs) of interventions intended to modify health behaviors may be influenced by neighborhood effects which can impede unbiased estimation of intervention effects. Examining a RCT designed to increase colorectal cancer (CRC) screening (N=5,628), we found statistically significant neighborhood effects: average CRC test use among neighboring study participants was significantly and positively associated with individual patient’s CRC test use. This potentially important spatially-varying covariate has not previously been considered in a RCT. Our results suggest that future RCTs of health behavior interventions should assess potential social interactions between participants, which may cause intervention arm contamination and may bias effect size estimation. PMID:25456014

  11. Randomized controlled trials in schizophrenia: opportunities, limitations, and trial design alternatives.

    PubMed

    Correll, Christoph U; Kishimoto, Taishiro; Kane, John M

    2011-01-01

    State-of-the art clinical trial design and methodology are enormously important for the advancement of the field. In contrast, the critical relevance of trial conduct and implementation have only more recently been the focus of discussion and research. Although randomized controlled trials are generally considered the gold standard for the assessment of pharmacologic and nonpharmacologic interventions in medicine, trials are vulnerable to complications and influences that can seriously compromise their success. Like interventions, trial design and conduct are also contextual. They need to be individualized and adapted to a number of relevant variables, such as setting, population, illness phase, interventions, patient and rater expectations and biases, and the overall aims of the investigation. While this means that there is no unified approach possible, certain general principles and guidelines require careful consideration. Knowledge of basic solutions and alternatives, and the recognition of the complex challenges that need to be addressed proactively can help to minimize unwanted outcomes, including trial failure and uninformative or falsely negative outcomes. Moreover, novel design alternatives need to be explored that target sample enrichment according to the study question and enhancement of precision in the measurement of relevant outcomes. We propose two novel design strategies that take advantage of the recently validated early antipsychotic response paradigm (that has also been observed with antidepressants and mood stabilizers). In the "early responder randomized discontinuation design" all patients are assigned to the active drug, and only those who had at least a minimal response at 2 weeks are enrolled in a double-blind, placebo-controlled discontinuation trial, enriching the placebo controlled trial portion with true drug responders. In the mirror image "early nonresponder randomized dose increase or augmentation design," early nonresponders at 2

  12. Randomized controlled trials in schizophrenia: opportunities, limitations, and trial design alternatives

    PubMed Central

    Correll, Christoph U.; Kishimoto, Taishiro; Kane, John M.

    2011-01-01

    State-of-the art clinical trial design and methodology are enormously important for the advancement of the field. In contrast, the critical relevance of trial conduct and implementation have only more recently been the focus of discussion and research. Although randomized controlled trials are generally considered the gold standard for the assessment of pharmacologic and nonpharmacologic interventions in medicine, trials are vulnerable to complications and influences that can seriously compromise their success, Like interventions, trial design and conduct are also contextual. They need to be individualized and adapted to a number of relevant variables, such as setting, population, illness phase, interventions, patient and rater expectations and biases, and the overall aims of the investigation. While this means that there is no unified approach possible, certain general principles and guidelines require careful consideration. Knowledge of basic solutions and alternatives, and the recognition of the complex challenges that need to be addressed proactively can help to minimize unwanted outcomes, including trial failure and uninformative or falsely negative outcomes. Moreover, novel design alternatives need to be explored that target sample enrichment according to the study question and enhancement of precision in the measurement of relevant outcomes. We propose two novel design strategies that take advantage of the recently validated early antipsychotic response paradigm (that has also been observed with antidepressants and mood stabilizers). In the “early responder randomized discontinuation design” all patients are assigned to the active drug, and only those who had at least a minimal response at 2 weeks are enrolled in a double-blind, placebo-controlled discontinuation trial, enriching the placebo controlled trial portion with true drug responders. In the mirror image “early nonresponder randomized dose increase or augmentation design,” early nonresponders

  13. Aromatherapy and behaviour disturbances in dementia: a randomized controlled trial.

    PubMed

    Smallwood, J; Brown, R; Coulter, F; Irvine, E; Copland, C

    2001-10-01

    A random controlled trial of the relaxing effects of an aromatherapy massage on disordered behaviour in dementia was conducted. Twenty-one patients were randomly allocated into one of three conditions, aromatherapy and massage (AM), conversation and aromatherapy (CA) and massage only (M). AM showed the greatest reduction in the frequency of excessive motor behaviour of all three conditions. This reached statistical significance between the hours of three and four pm (p < 0.05). Post hoc analysis suggested that at this time of day the AM consistently reduced motor behaviour when compared with CA (p = 0.05). This provides preliminary evidence of a measurable sedative effect of aromatherapy massage on dementia within a robust scientific paradigm. Further research is recommended with an expanded sample size. PMID:11607948

  14. Randomized, Controlled Trial of an Intervention for Toddlers With Autism: The Early Start Denver Model

    PubMed Central

    Dawson, Geraldine; Rogers, Sally; Munson, Jeffrey; Smith, Milani; Winter, Jamie; Greenson, Jessica; Donaldson, Amy; Varley, Jennifer

    2016-01-01

    OBJECTIVE To conduct a randomized, controlled trial to evaluate the efficacy of the Early Start Denver Model (ESDM), a comprehensive developmental behavioral intervention, for improving outcomes of toddlers diagnosed with autism spectrum disorder (ASD). METHODS Forty-eight children diagnosed with ASD between 18 and 30 months of age were randomly assigned to 1 of 2 groups: (1) ESDM intervention, which is based on developmental and applied behavioral analytic principles and delivered by trained therapists and parents for 2 years; or (2) referral to community providers for intervention commonly available in the community. RESULTS Compared with children who received community-intervention, children who received ESDM showed significant improvements in IQ, adaptive behavior, and autism diagnosis. Two years after entering intervention, the ESDM group on average improved 17.6 standard score points (1 SD:15 points) compared with 7.0 points in the comparison group relative to baseline scores. The ESDM group maintained its rate of grow thin adaptive behavior compared with a normative sample of typically developing children. In contrast, over the 2-year span, the comparison group showed greater delays in adaptive behavior. Children who received ESDM also were more likely to experience a change in diagnosis from autism to pervasive developmental disorder, not otherwise specified, than the comparison group. CONCLUSIONS This is the first randomized, controlled trial to demonstrate the efficacy of a comprehensive developmental behavioral intervention for toddlers with ASD for improving cognitive and adaptive behavior and reducing severity of ASD diagnosis. Results of this study underscore the importance of early detection of and intervention in autism. PMID:19948568

  15. A sensitivity analysis of the Children’s Treatment Network trial: a randomized controlled trial of integrated services versus usual care for children with special health care needs

    PubMed Central

    Ye, Chenglin; Browne, Gina; Beyene, Joseph; Thabane, Lehana

    2013-01-01

    Background The value of integrated care through comprehensive, coordinated, and family-centered services has been increasingly recognized for improving health outcomes of children with special health care needs (CSHCN). In a randomized controlled trial (RCT), the integrated care provided through the Children’s Treatment Network (CTN) was compared with usual care in improving the psychosocial health of target CSHCN. In this paper, we aimed to estimate the effect of CTN care by conducting multiple analyses to handle noncompliance in the trial. Methods The trial recruited target children in Simcoe County and York Region, ON, Canada. Children were randomized to receive CTN or usual care and were followed for 2 years. The CTN group received integrated services through multiple providers to address their specific needs while the usual care group continued to receive care directed by their parents. The outcome was change in psychosocial quality of life at 2 years. We conducted intention-to-treat, as-treated, per-protocol, and instrumental variable analyses to analyze the outcome. Results The trial randomized 445 children, with 229 in the intervention group and 216 in the control group. During follow-up, 52% of children in the intervention group did not receive complete CTN care for various reasons. At 2 years, we did not find a significant improvement in psychosocial quality of life among the children receiving CTN care compared with usual care (intention-to-treat mean difference 1.50, 95% confidence interval −1.49 to 4.50; P = 0.32). Other methods of analysis yielded similar results. Conclusion Although the effect of CTN care was not significant, there was evidence showing benefits of integrated care for CSHCN. More RCTs are needed to demonstrate the magnitude of such an effect. The CTN study highlights the key challenges in RCTs when assessing interventions involving integrated care, and informs further RCTs including similar evaluations. PMID:24098089

  16. The Ethics of Randomized Controlled Trials in Social Settings: Can Social Trials Be Scientifically Promising and Must There Be Equipoise?

    ERIC Educational Resources Information Center

    Fives, Allyn; Russell, Daniel W.; Canavan, John; Lyons, Rena; Eaton, Patricia; Devaney, Carmel; Kearns, Norean; O'Brien, Aoife

    2015-01-01

    In a randomized controlled trial (RCT), treatments are assigned randomly and treatments are withheld from participants. Is it ethically permissible to conduct an RCT in a social setting? This paper addresses two conditions for justifying RCTs: that there should be a state of equipoise and that the trial should be scientifically promising.…

  17. Incorporating Contact Network Structure in Cluster Randomized Trials

    NASA Astrophysics Data System (ADS)

    Staples, Patrick C.; Ogburn, Elizabeth L.; Onnela, Jukka-Pekka

    2015-12-01

    Whenever possible, the efficacy of a new treatment is investigated by randomly assigning some individuals to a treatment and others to control, and comparing the outcomes between the two groups. Often, when the treatment aims to slow an infectious disease, clusters of individuals are assigned to each treatment arm. The structure of interactions within and between clusters can reduce the power of the trial, i.e. the probability of correctly detecting a real treatment effect. We investigate the relationships among power, within-cluster structure, cross-contamination via between-cluster mixing, and infectivity by simulating an infectious process on a collection of clusters. We demonstrate that compared to simulation-based methods, current formula-based power calculations may be conservative for low levels of between-cluster mixing, but failing to account for moderate or high amounts can result in severely underpowered studies. Power also depends on within-cluster network structure for certain kinds of infectious spreading. Infections that spread opportunistically through highly connected individuals have unpredictable infectious breakouts, making it harder to distinguish between random variation and real treatment effects. Our approach can be used before conducting a trial to assess power using network information, and we demonstrate how empirical data can inform the extent of between-cluster mixing.

  18. Incorporating Contact Network Structure in Cluster Randomized Trials.

    PubMed

    Staples, Patrick C; Ogburn, Elizabeth L; Onnela, Jukka-Pekka

    2015-01-01

    Whenever possible, the efficacy of a new treatment is investigated by randomly assigning some individuals to a treatment and others to control, and comparing the outcomes between the two groups. Often, when the treatment aims to slow an infectious disease, clusters of individuals are assigned to each treatment arm. The structure of interactions within and between clusters can reduce the power of the trial, i.e. the probability of correctly detecting a real treatment effect. We investigate the relationships among power, within-cluster structure, cross-contamination via between-cluster mixing, and infectivity by simulating an infectious process on a collection of clusters. We demonstrate that compared to simulation-based methods, current formula-based power calculations may be conservative for low levels of between-cluster mixing, but failing to account for moderate or high amounts can result in severely underpowered studies. Power also depends on within-cluster network structure for certain kinds of infectious spreading. Infections that spread opportunistically through highly connected individuals have unpredictable infectious breakouts, making it harder to distinguish between random variation and real treatment effects. Our approach can be used before conducting a trial to assess power using network information, and we demonstrate how empirical data can inform the extent of between-cluster mixing. PMID:26631604

  19. Mini vs. Standard Implants for Mandibular Overdentures: A Randomized Trial.

    PubMed

    de Souza, R F; Ribeiro, A B; Della Vecchia, M P; Costa, L; Cunha, T R; Reis, A C; Albuquerque, R F

    2015-10-01

    A mandibular implant-retained overdenture is considered a first-choice treatment for edentulism. However, some aspects limit the use of standard implants-for example, the width of edentulous ridges, chronic diseases, fear, or costs. This randomized trial compared mandibular overdentures retained by 2 or 4 mini-implants with standard implants, considering oral health-related quality of life (OHRQoL), patient satisfaction, and complications such as lost implant. In sum, 120 edentulous men and women (mean age, 59.5 ± 8.5 y) randomly received 4 mini-implants, 2 mini-implants, or 2 standard implants. Participants provided data regarding OHRQoL and satisfaction until 12 mo. Clinical parameters, including implant survival rate, were also recorded. Both 2 and 4 mini-implants led to better OHRQoL, compared with 2 standard implants. Treatment with 4 mini-implants was more satisfying than 2 standard implants, with 2 mini-implants presenting intermediate results. Implant survival rate was 89%, 82%, and 99% for 4 mini-implants, 2 mini-implants, or 2 standard implants, respectively. Overdentures retained by 4 or 2 mini-implants can achieve OHRQoL and satisfaction at least comparable with that of 2 standard implants. However, the survival rate of mini implants is not as high as that of standard implants (ClinicalTrials.gov NCT01411683). PMID:26294416

  20. Reiki for the Treatment of Fibromyalgia: A Randomized Controlled Trial

    PubMed Central

    Assefi, Nassim; Bogart, Andy; Goldberg, Jack

    2008-01-01

    Abstract Objective Fibromyalgia is a common, chronic pain condition for which patients frequently use complementary and alternative medicine, including Reiki. Our objective was to determine whether Reiki is beneficial as an adjunctive fibromyalgia treatment. Design This was a factorial designed, randomized, sham-controlled trial in which participants, data collection staff, and data analysts were blinded to treatment group. Setting/location The study setting was private medical offices in the Seattle, Washington metropolitan area. Subjects The subjects were comprised 100 adults with fibromyalgia. Intervention Four (4) groups received twice-weekly treatment for 8 weeks by either a Reiki master or actor randomized to use direct touch or no touch (distant therapy). Outcome measures The primary outcome was subjective pain as measured by visual analog scale at weeks 4, 8, and 20 (3 months following end of treatment). Secondary outcomes were physical and mental functioning, medication use, and health provider visits. Participant blinding and adverse effects were ascertained by selfreport. Improvement between groups was examined in an intention-to-treat analysis. Results Neither Reiki nor touch had any effect on pain or any of the secondary outcomes. All outcome measures were nearly identical among the 4 treatment groups during the course of the trial. Conclusion Neither Reiki nor touch improved the symptoms of fibromyalgia. Energy medicine modalities such as Reiki should be rigorously studied before being recommended to patients with chronic pain symptoms. PMID:18991519

  1. Tooth-surface-specific effects of xylitol: randomized trial results.

    PubMed

    Ritter, A V; Bader, J D; Leo, M C; Preisser, J S; Shugars, D A; Vollmer, W M; Amaechi, B T; Holland, J C

    2013-06-01

    The Xylitol for Adult Caries Trial was a three-year, double-blind, multi-center, randomized clinical trial that evaluated the effectiveness of xylitol vs. placebo lozenges in the prevention of dental caries in caries-active adults. The purpose of this secondary analysis was to investigate whether xylitol lozenges had a differential effect on cumulative caries increments on different tooth surfaces. Participants (ages 21-80 yrs) with at least one follow-up visit (n = 620) were examined at baseline, 12, 24, and 33 months. Negative binomial and zero-inflated negative binomial regression models were used to estimate incidence rate ratios (IRR) for xylitol's differential effect on cumulative caries increments on root and coronal surfaces and, among coronal surfaces, on smooth (buccal and lingual), occlusal, and proximal surfaces. Participants in the xylitol arm developed 40% fewer root caries lesions (0.23 D2FS/year) than those in the placebo arm (0.38 D2FS/year; IRR = 0.60; 95% CI [0.44, 0.81]; p < .001). There was no statistically significant difference between xylitol and control participants in the incidence of smooth-surface caries (p = .100), occlusal-surface caries (p = .408), or proximal-surface caries (p = .159). Among these caries-active adults, xylitol appears to have a caries-preventive effect on root surfaces (ClinicalTrials.gov NCT00393055). PMID:23589387

  2. Randomized Polypill Crossover Trial in People Aged 50 and Over

    PubMed Central

    Wald, David S.; Morris, Joan K.; Wald, Nicholas J.

    2012-01-01

    Background A Polypill is proposed for the primary prevention of cardiovascular disease in people judged to be at risk on account of their age alone. Its efficacy in reducing cholesterol and blood pressure is uncertain. Methods We conducted a randomized double-blind placebo-controlled crossover trial of a Polypill among individuals aged 50+ without a history of cardiovascular disease and compared the reductions with those predicted from published estimates of the effects of the individual drugs. Participants took the Polypill (amlodipine 2.5 mg, losartan 25 mg, hydrochlorothiazide 12.5 mg and simvastatin 40 mg) each evening for 12 weeks and a placebo each evening for 12 weeks in random sequence. The mean within-person differences in blood pressure and low density lipoprotein (LDL) cholesterol at the end of each 12 week period were determined. Results 84 out of 86 participants completed both treatment periods. The mean systolic blood pressure was reduced by 17.9 mmHg (95% CI, 15.7–20.1) on the Polypill, diastolic blood pressure by 9.8 mmHg (8.1–11.5), and LDL cholesterol by 1.4 mmol/L (1.2–1.6), reductions of 12%, 11%, and 39% respectively. The results were almost identical to those predicted; 18.4 mmHg, 9.7 mmHg, and 1.4 mmol/L respectively. Conclusion The Polypill resulted in the predicted reductions in blood pressure and LDL cholesterol. Long term reductions of this magnitude would have a substantial effect in preventing heart attacks and strokes. Trial Registration Controlled-Trials.com ISRCTN36672232 PMID:22815989

  3. The Cessation in Pregnancy Incentives Trial (CPIT): study protocol for a randomized controlled trial

    PubMed Central

    2012-01-01

    Background Seventy percent of women in Scotland have at least one baby, making pregnancy an opportunity to help most young women quit smoking before their own health is irreparably compromised. By quitting during pregnancy their infants will be protected from miscarriage and still birth as well as low birth weight, asthma, attention deficit disorder and adult cardiovascular disease. In the UK, the NICE guidelines: ‘How to stop smoking in pregnancy and following childbirth’ (June 2010) highlighted that little evidence exists in the literature to confirm the efficacy of financial incentives to help pregnant smokers to quit. Its first research recommendation was to determine: Within a UK context, are incentives an acceptable, effective and cost-effective way to help pregnant women who smoke to quit? Design and methods This study is a phase II exploratory individually randomized controlled trial comparing standard care for pregnant smokers with standard care plus the additional offer of financial voucher incentives to engage with specialist cessation services and/or to quit smoking during pregnancy. Participants (n = 600) will be pregnant smokers identified at maternity booking who, when contacted by specialist cessation services, agree to having their details passed to the NHS Smokefree Pregnancy Study Helpline to discuss the trial. The NHS Smokefree Pregnancy Study Helpline will be responsible for telephone consent and follow-up in late pregnancy. The primary outcome will be self reported smoking in late pregnancy verified by cotinine measurement. An economic evaluation will refine cost data collection and assess potential cost-effectiveness while qualitative research interviews with clients and health professionals will assess the level of acceptance of this form of incentive payment. The research questions are: What is the likely therapeutic efficacy? Are incentives potentially cost-effective? Is individual randomization an efficient trial design without

  4. Effect of vitamin D supplementation on progression of knee pain and cartilage volume loss in patients with symptomatic osteoarthritis: a randomized controlled trial

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Knee osteoarthritis (OA), a disorder of cartilage and periarticular bone, is a public health problem without effective medical treatments. Some studies have suggested that vitamin D may protect against structural progression. A 2-year randomized, placebo-controlled, double-blind, clinical trial invo...

  5. Randomized Trial of Reduced-Nicotine Standards for Cigarettes

    PubMed Central

    Donny, Eric C.; Denlinger, Rachel L.; Tidey, Jennifer W.; Koopmeiners, Joseph S.; Benowitz, Neal L.; Vandrey, Ryan G.; al’Absi, Mustafa; Carmella, Steven G.; Cinciripini, Paul M.; Dermody, Sarah S.; Drobes, David J.; Hecht, Stephen S.; Jensen, Joni; Lane, Tonya; Le, Chap T.; McClernon, F. Joseph; Montoya, Ivan D.; Murphy, Sharon E.; Robinson, Jason D.; Stitzer, Maxine L.; Strasser, Andrew A.; Tindle, Hilary; Hatsukami, Dorothy K.

    2015-01-01

    BACKGROUND The Food and Drug Administration can set standards that reduce the nicotine content of cigarettes. METHODS We conducted a double-blind, parallel, randomized clinical trial between June 2013 and July 2014 at 10 sites. Eligibility criteria included an age of 18 years or older, smoking of five or more cigarettes per day, and no current interest in quitting smoking. Participants were randomly assigned to smoke for 6 weeks either their usual brand of cigarettes or one of six types of investigational cigarettes, provided free. The investigational cigarettes had nicotine content ranging from 15.8 mg per gram of tobacco (typical of commercial brands) to 0.4 mg per gram. The primary outcome was the number of cigarettes smoked per day during week 6. RESULTS A total of 840 participants underwent randomization, and 780 completed the 6-week study. During week 6, the average number of cigarettes smoked per day was lower for participants randomly assigned to cigarettes containing 2.4, 1.3, or 0.4 mg of nicotine per gram of tobacco (16.5, 16.3, and 14.9 cigarettes, respectively) than for participants randomly assigned to their usual brand or to cigarettes containing 15.8 mg per gram (22.2 and 21.3 cigarettes, respectively; P<0.001). Participants assigned to cigarettes with 5.2 mg per gram smoked an average of 20.8 cigarettes per day, which did not differ significantly from the average number among those who smoked control cigarettes. Cigarettes with lower nicotine content, as compared with control cigarettes, reduced exposure to and dependence on nicotine, as well as craving during abstinence from smoking, without significantly increasing the expired carbon monoxide level or total puff volume, suggesting minimal compensation. Adverse events were generally mild and similar among groups. CONCLUSIONS In this 6-week study, reduced-nicotine cigarettes versus standard-nicotine cigarettes reduced nicotine exposure and dependence and the number of cigarettes smoked. (Funded by

  6. The Sexunzipped Trial: Optimizing the Design of Online Randomized Controlled Trials

    PubMed Central

    Pavlou, Menelaos; Copas, Andrew; McCarthy, Ona; Carswell, Ken; Rait, Greta; Hart, Graham; Nazareth, Irwin; Free, Caroline; French, Rebecca; Murray, Elizabeth

    2013-01-01

    Background Sexual health problems such as unwanted pregnancy and sexually transmitted infection are important public health concerns and there is huge potential for health promotion using digital interventions. Evaluations of digital interventions are increasingly conducted online. Trial administration and data collection online offers many advantages, but concerns remain over fraudulent registration to obtain compensation, the quality of self-reported data, and high attrition. Objective This study addresses the feasibility of several dimensions of online trial design—recruitment, online consent, participant identity verification, randomization and concealment of allocation, online data collection, data quality, and retention at 3-month follow-up. Methods Young people aged 16 to 20 years and resident in the United Kingdom were recruited to the “Sexunzipped” online trial between November 2010 and March 2011 (n=2036). Participants filled in baseline demographic and sexual health questionnaires online and were randomized to the Sexunzipped interactive intervention website or to an information-only control website. Participants were also randomly allocated to a postal request (or no request) for a urine sample for genital chlamydia testing and receipt of a lower (£10/US$16) or higher (£20/US$32) value shopping voucher compensation for 3-month outcome data. Results The majority of the 2006 valid participants (90.98%, 1825/2006) were aged between 18 and 20 years at enrolment, from all four countries in the United Kingdom. Most were white (89.98%, 1805/2006), most were in school or training (77.48%, 1545/1994), and 62.81% (1260/2006) of the sample were female. In total, 3.88% (79/2036) of registrations appeared to be invalid and another 4.00% (81/2006) of participants gave inconsistent responses within the questionnaire. The higher value compensation (£20/US$32) increased response rates by 6-10%, boosting retention at 3 months to 77.2% (166/215) for submission of

  7. Acupuncture for Vascular Dementia: A Pragmatic Randomized Clinical Trial

    PubMed Central

    Shi, Guang-Xia; Li, Qian-Qian; Yang, Bo-Feng; Liu, Yan; Guan, Li-Ping; Wu, Meng-Meng; Wang, Lin-Peng; Liu, Cun-Zhi

    2015-01-01

    In this trial, patients who agreed to random assignment were allocated to a randomized acupuncture group (R-acupuncture group) or control group. Those who declined randomization were assigned to a nonrandomized acupuncture group (NR-acupuncture group). Patients in the R-acupuncture group and NR-acupuncture group received up to 21 acupuncture sessions during a period of 6 weeks plus routine care, while the control group received routine care alone. Cognitive function, activities of daily living, and quality of life were assessed by mini-mental state examination (MMSE), Activities of Daily Living Scale (ADL), and dementia quality of life questionnaire (DEMQOL), respectively. All the data were collected at baseline, after 6-week treatment, and after 4-week follow-up. No significant differences of MMSE scores were observed among the three groups but pooled-acupuncture group had significant higher score than control group. Compared to control group, ADL score significantly decreased in NR-acupuncture group and pooled-acupuncture group. For DEMQOL scores, no significant differences were observed among the three groups, as well as between pooled-acupuncture group and control group. Additional acupuncture to routine care may have beneficial effects on the improvements of cognitive status and activities of daily living but have limited efficacy on health-related quality of life in VaD patients. PMID:26495416

  8. Cervical Lidocaine for IUD Insertional Pain: a Randomized Controlled Trial

    PubMed Central

    McNicholas, Colleen P.; Madden, Tessa; Zhao, Qiuhong; Secura, Gina; Allsworth, Jenifer E.; Peipert, Jeffrey F.

    2012-01-01

    Objective Anticipated pain with intrauterine device (IUD) insertion may be a barrier to widespread use. Our objective was to evaluate the efficacy of intracervical 2% lidocaine gel for pain relief with IUD insertion. Study Design We performed a double-blind, randomized controlled trial of women undergoing IUD insertion. Participants were randomly assigned to 2% lidocaine or placebo gel. Study gel (3ccs) wase placed 3 minutes prior to IUD insertion. Pain scores were measured at various time points using a 10-point visual analog scale. Results Of the 200 participants randomized, 199 completed the study. Pain scores among lidocaine and placebo arms were similar at tenaculum placement (lidocaine and placebo; median 4, range 0–10 p=0.15) as well as with insertion (lidocaine: median 5 range 1–10, placebo: median 6 range 0–10 p=0.16). These results did not differ by parity. Conclusions Topical or intracervical 2% lidocaine gel prior to IUD insertion does not decrease pain scores. PMID:23107081

  9. Medication reconciliation at patient admission: a randomized controlled trial

    PubMed Central

    Mendes, Antonio E.; Lombardi, Natália F.; Andrzejevski, Vânia S.; Frandoloso, Gibran; Correr, Cassyano J.; Carvalho, Mauricio

    2015-01-01

    Objective: To measure length of hospital stay (LHS) in patients receiving medication reconciliation. Secondary characteristics included analysis of number of preadmission medications, medications prescribed at admission, number of discrepancies, and pharmacists interventions done and accepted by the attending physician. Methods: A 6 month, randomized, controlled trial conducted at a public teaching hospital in southern Brazil. Patients admitted to general wards were randomized to receive usual care or medication reconciliation, performed within the first 72 hours of hospital admission. Results: The randomization process assigned 68 patients to UC and 65 to MR. LHS was 10±15 days in usual care and 9±16 days in medication reconciliation (p=0.620). The total number of discrepancies was 327 in the medication reconciliation group, comprising 52.6% of unintentional discrepancies. Physicians accepted approximately 75.0% of the interventions. Conclusion: These results highlight weakness at patient transition care levels in a public teaching hospital. LHS, the primary outcome, should be further investigated in larger studies. Medication reconciliation was well accepted by physicians and it is a useful tool to find and correct discrepancies, minimizing the risk of adverse drug events and improving patient safety. PMID:27011775

  10. Using Vascular Quality Initiative as a Platform for Organizing Multicenter, Prospective, Randomized Clinical Trials: OVERPAR Trial

    PubMed Central

    Eslami, Mohammad H.; Doros, Gheorghe; Goodney, Philip P.; Elderup-Jorgenson, Jens; Cronenwett, Jack L.; Malikova, Marina; Farber, Alik

    2014-01-01

    Background We describe the organization of a prospective, randomized, multicenter trial comparing the effectiveness of open popliteal artery aneurysm repair (OPAR) and endovascular popliteal artery aneurysm repair (EPAR) of asymptomatic popliteal artery aneurysms (PAAs) as an example for how to use the Vascular Quality Initiative (VQI) framework. Given that many centers participate in the VQI, this model can be used to perform multicenters’ prospective trials on very modest budget. Methods VQI prospectively collects data on many vascular procedures. These data include many important perioperative, intraoperative, and postoperative details regarding both patients and their procedures. We describe a study where minimal changes to the collected data by participating centers can provide level-1 evidence regarding a significant clinical question. Data will be collected using modified VQI forms within the existing VQI data reporting structure. We plan to enroll 148 patients with asymptomatic PAAs into the open and endovascular surgery cohorts. Patients from participating VQI centers will be randomized 1:1 to either OPAR or EPAR and will be followed for an average of 2.5 years. Our primary hypothesis is that major adverse limb event–free survival is lower in the EPAR cohort and that EPAR is associated with more secondary interventions, improved quality of life, and decreased length of stay. The budget for this trial is fixed at $10,000/year for the course of the study, and the trial is judged to be feasible because of the functionality of the VQI platform. Conclusions Using the existing VQI infrastructure, Open versus Endovascular Repair of Popliteal Artery Aneurysm will provide level 1 data for PAA treatment on a modest budget. The proposed trial has an adequately powered comparative design that will use objective performance goals to describe limb-related morbidity and procedural reintervention rates. PMID:25311746

  11. A Randomized Controlled Trial of Mindfulness Meditation for Chronic Insomnia

    PubMed Central

    Ong, Jason C.; Manber, Rachel; Segal, Zindel; Xia, Yinglin; Shapiro, Shauna; Wyatt, James K.

    2014-01-01

    Study Objectives: To evaluate the efficacy of mindfulness meditation for the treatment of chronic insomnia. Design: Three-arm, single-site, randomized controlled trial. Setting: Academic medical center. Participants: Fifty-four adults with chronic insomnia. Interventions: Participants were randomized to either mindfulness-based stress reduction (MBSR), mindfulness-based therapy for insomnia (MBTI), or an eight-week self-monitoring (SM) condition. Measurements and Results: Patient-reported outcome measures were total wake time (TWT) from sleep diaries, the pre-sleep arousal scale (PSAS), measuring a prominent waking correlate of insomnia, and the Insomnia Severity Index (ISI) to determine remission and response as clinical endpoints. Objective sleep measures were derived from laboratory polysomnography and wrist actigraphy. Linear mixed models showed that those receiving a meditation-based intervention (MBSR or MBTI) had significantly greater reductions on TWT minutes (43.75 vs 1.09), PSAS (7.13 vs 0.16), and ISI (4.56 vs 0.06) from baseline-to-post compared to SM. Post hoc analyses revealed that each intervention was superior to SM on each of the patient-reported measures, but no significant differences were found when comparing MBSR to MBTI from baseline-to-post. From baseline to 6-month follow-up, MBTI had greater reductions in ISI scores than MBSR (P < 0.05), with the largest difference occurring at the 3-month follow-up. Remission and response rates in MBTI and MBSR were sustained from post-treatment through follow-up, with MBTI showing the highest rates of treatment remission (50%) and response (78.6%) at the 6-month follow-up. Conclusions: Mindfulness meditation appears to be a viable treatment option for adults with chronic insomnia and could provide an alternative to traditional treatments for insomnia. Trial Registration: Mindfulness-Based Approaches to Insomnia: clinicaltrials.gov, identifier: NCT00768781 Citation: Ong JC, Manber R, Segal Z, Xia Y

  12. Sequential multiple assignment randomized trial (SMART) with adaptive randomization for quality improvement in depression treatment program.

    PubMed

    Cheung, Ying Kuen; Chakraborty, Bibhas; Davidson, Karina W

    2015-06-01

    Implementation study is an important tool for deploying state-of-the-art treatments from clinical efficacy studies into a treatment program, with the dual goals of learning about effectiveness of the treatments and improving the quality of care for patients enrolled into the program. In this article, we deal with the design of a treatment program of dynamic treatment regimens (DTRs) for patients with depression post-acute coronary syndrome. We introduce a novel adaptive randomization scheme for a sequential multiple assignment randomized trial of DTRs. Our approach adapts the randomization probabilities to favor treatment sequences having comparatively superior Q-functions used in Q-learning. The proposed approach addresses three main concerns of an implementation study: it allows incorporation of historical data or opinions, it includes randomization for learning purposes, and it aims to improve care via adaptation throughout the program. We demonstrate how to apply our method to design a depression treatment program using data from a previous study. By simulation, we illustrate that the inputs from historical data are important for the program performance measured by the expected outcomes of the enrollees, but also show that the adaptive randomization scheme is able to compensate poorly specified historical inputs by improving patient outcomes within a reasonable horizon. The simulation results also confirm that the proposed design allows efficient learning of the treatments by alleviating the curse of dimensionality. PMID:25354029

  13. Down syndrome and dementia: a randomized, controlled trial of antioxidant supplementation.

    PubMed

    Lott, Ira T; Doran, Eric; Nguyen, Vinh Q; Tournay, Anne; Head, Elizabeth; Gillen, Daniel L

    2011-08-01

    Individuals with Down syndrome over age 40 years are at risk for developing dementia of the Alzheimer type and have evidence for chronic oxidative stress. There is a paucity of treatment trials for dementia in Down syndrome in comparison to Alzheimer disease in the general (non-Down syndrome) population. This 2-year randomized, double-blind, placebo-controlled trial assessed whether daily oral antioxidant supplementation (900 IU of alpha-tocopherol, 200 mg of ascorbic acid and 600 mg of alpha-lipoic acid) was effective, safe and tolerable for 53 individuals with Down syndrome and dementia. The outcome measures comprised a battery of neuropsychological assessments administered at baseline and every 6 months. Compared to the placebo group, those individuals receiving the antioxidant supplement showed neither an improvement in cognitive functioning nor a stabilization of cognitive decline. Mean plasma levels of alpha-tocopherol increased ~2-fold in the treatment group and were consistently higher than the placebo group over the treatment period. Pill counts indicated good compliance with the regimen. No serious adverse events attributed to the treatment were noted. We conclude that antioxidant supplementation is safe, though ineffective as a treatment for dementia in individuals with Down syndrome and Alzheimer type dementia. Our findings are similar to studies of antioxidant supplementation in Alzheimer disease in the general population. The feasibility of carrying out a clinical trial for dementia in Down syndrome is demonstrated. PMID:21739598

  14. Vitamin D supplementation in the management of knee osteoarthritis: study protocol for a randomized controlled trial

    PubMed Central

    2012-01-01

    Background Osteoarthritis (OA) is a common health issue worldwide in the aging population who are also commonly deficient in vitamin D. Our previous study suggested that higher serum 25-(OH)D levels were associated with reduced knee cartilage loss, implying that vitamin D supplementation may prevent the progression of knee OA. The aim of the VItamin D Effects on OA (VIDEO) study is to compare, over a 2- year period, the effects of vitamin D supplementation versus placebo on knee structural changes, knee pain, and lower limb muscle strength in patients with symptomatic knee OA. Methods/design Randomised, placebo-controlled, and double-blind clinical trial aiming to recruit 400 subjects (200 from Tasmania and 200 from Victoria) with both symptomatic knee OA and vitamin D deficiency (serum [25-(OH)D] level of >12.5 nmol/liter and <60 nmol/liter). Participants will be randomly allocated to vitamin D supplementation (50,000 IU compounded vitamin D3 capsule monthly) or identical inert placebo group for 2 years. The primary endpoint is loss of knee cartilage volume measured by magnetic resonance imaging (MRI) and Western Ontario and McMaster Universities Index of OA (WOMAC) knee pain score. The secondary endpoints will be other knee structural changes, and lower limb muscle strength. Several other outcome measures including core muscle images and central blood pressure will be recorded. Linear and logistic regression will be used to compare changes between groups using univariable and multivariable modeling analyses. Both intention to treat and per protocol analyses will be utilized. Discussion The trial is designed to test if vitamin D supplementation will reduce loss of knee cartilage volume, prevent the progression of other knee structural abnormalities, reduce knee pain and strengthen lower limb muscle strength, thus modify disease progression in knee OA. Trial registration ClinicalTrials.gov identifier: NCT01176344; Australian New Zealand Clinical Trials

  15. Cognitive Stimulation in Patients with Dementia: Randomized Controlled Trial

    PubMed Central

    Mapelli, Daniela; Di Rosa, Elisa; Nocita, Rosaria; Sava, Donatella

    2013-01-01

    Background/Aims This study explores the effective outcomes of a structured cognitive stimulation treatment to improve cognition and behavioral symptoms in people with dementia (PWDs), using a randomized controlled clinical trial. Methods Thirty PWDs were divided into three groups: experimental (treated with cognitive stimulation), placebo (treated with occupational therapy), and control (continuing with the usual activities of the nursing home). Assessment, at baseline and after a period of 8 weeks, was performed using the Clinical Dementia Rating Scale, activities of daily living, Mini-Mental State Examination, Esame Neuropsicologico Breve 2, Geriatric Depression Scale and Behavioral Pathology in Alzheimer's Disease Scale. Results Only the experimental group improved its performance in cognitive tests (p < 0.05) and showed a significant decrease in behavioral symptoms (p < 0.01) after the treatment. Conclusions The results suggest that a cognitive stimulation treatment for PWDs would improve not only their cognition, but also behavioral symptoms. PMID:24052800

  16. A randomized controlled trial of analgesia during vaccination in adults.

    PubMed

    Taddio, Anna; Lord, Allison; Hogan, Mary-Ellen; Kikuta, Andrew; Yiu, Ashley; Darra, Erwin; Bruinse, Barbara; Keogh, Tom; Stephens, Derek

    2010-07-19

    Although immunization injections are the most common painful medical procedures, pain-relieving interventions are not routinely used. In this randomized controlled trial, we compared the effectiveness of topical anesthesia using liposomal lidocaine to: (1) vapocoolant spray using a proprietary blend of 1,1,1,3,3-pentafluoropropane and 1,1,1,2-tetrafluoroethane; (2) nurse-administered tactile stimulation; or (3) self-directed distraction by means of reading a magazine. Liposomal lidocaine was more effective (p

  17. [Critical of the additive model of the randomized controlled trial].

    PubMed

    Boussageon, Rémy; Gueyffier, François; Bejan-Angoulvant, Theodora; Felden-Dominiak, Géraldine

    2008-01-01

    Randomized, double-blind, placebo-controlled clinical trials are currently the best way to demonstrate the clinical effectiveness of drugs. Its methodology relies on the method of difference (John Stuart Mill), through which the observed difference between two groups (drug vs placebo) can be attributed to the pharmacological effect of the drug being tested. However, this additive model can be questioned in the event of statistical interactions between the pharmacological and the placebo effects. Evidence in different domains has shown that the placebo effect can influence the effect of the active principle. This article evaluates the methodological, clinical and epistemological consequences of this phenomenon. Topics treated include extrapolating results, accounting for heterogeneous results, demonstrating the existence of several factors in the placebo effect, the necessity to take these factors into account for given symptoms or pathologies, as well as the problem of the "specific" effect. PMID:18387273

  18. The conflict between randomized clinical trials and the therapeutic obligation.

    PubMed

    Gifford, F

    1986-11-01

    The central dilemma concerning randomized clinical trials (RCTs) arises out of some simple facts about causal methodology (RCTs are the best way to generate the reliable causal knowledge necessary for optimally-informed action) and a prima facie plausible principle concerning how physicians should treat their patients (always do what it is most reasonable to believe will be best for the patient). A number of arguments related to this in the literature are considered. Attempts to avoid the dilemma fail. Appeals to informed consent and mechanisms for minimizing the resulting harm are important for policy, but informed consent is problematic and mechanisms for minimization of harm do not address the dilemma. Appeals to some sort of contract model of justification are promising and illuminating. PMID:3819604

  19. A randomized trial on root caries prevention in elders.

    PubMed

    Tan, H P; Lo, E C M; Dyson, J E; Luo, Y; Corbet, E F

    2010-10-01

    Root caries is common in institutionalized elders, and effective prevention methods are needed. This clinical trial compared the effectiveness of four methods in preventing new root caries. From 21 residential homes, 306 generally healthy elders having at least 5 teeth with exposed sound root surfaces were randomly allocated into one of four groups: (1) individualized oral hygiene instruction (OHI); (2) OHI and applications of 1% chlorhexidine varnish every 3 months; (3) OHI and applications of 5% sodium fluoride varnish every 3 months; and (4) OHI and annual applications of 38% silver diamine fluoride (SDF) solution. Two-thirds (203/306) of the elders were followed for 3 years. Mean numbers of new root caries surfaces in the four groups were 2.5, 1.1, 0.9, and 0.7, respectively (ANOVA, p < 0.001). SDF solution, sodium fluoride varnish, and chlorhexidine varnish were more effective in preventing new root caries than giving OHI alone. PMID:20671206

  20. Randomized Trial of Intensive Motivational Interviewing for Methamphetamine Dependence

    PubMed Central

    Polcin, Douglas L.; Bond, Jason; Korcha, Rachael; Nayak, Madhabika B.; Galloway, Gantt P.; Evans, Kristy

    2014-01-01

    An intensive, 9-session Motivational Interviewing (IMI) intervention was assessed using a randomized clinical trial of 217 methamphetamine (MA) dependent persons. Intensive motivational interviewing (IMI) was compared with a standard single standard session of MI (SMI) combined with eight nutrition education sessions. Interventions were delivered weekly over two months. All study participants also received standard outpatient group treatment three times per week. Both study conditions showed significant decreases in MA use and ASI drug scores, but there were no significant differences between the two conditions. However, reductions in ASI psychiatric severity scores and days of psychiatric problems during the past 30 days were found for clients in the IMI condition but not SMI. SMI may be equally beneficial to IMI in reducing MA use and problem severity, but IMI may help alleviate co-occurring psychiatric problems that are unaffected by shorter MI interventions. Additional studies are needed to assess the problems, populations, and contexts for which IMI is effective. PMID:25115166

  1. Ethical Considerations for Conducting a Randomized Controlled Trial in Transport

    PubMed Central

    Reimer, Andrew P.; Daly, Barbara J.

    2014-01-01

    Although recent studies support the rapid transfer of patients experiencing time-sensitive emergencies, limited data exist to support the use of air transport for non-urgent patient transfers. The nature of medical transport and the heterogeneity of patients who are transferred present unique challenges in designing and conducting clinical research trials that could contribute to the evidence-based decision-making for patient care and transport. The current regulatory framework presents several barriers to conducting such research in the medical transport setting. We present a hypothetical study that randomizes patients to either ground or air transport as an exemplar. We discuss informed consent, risk, and the impracticality of conducting community consultations in a medical transport setting. Finally, recommendations for potential changes to current regulations are presented. These are directed at facilitating the conduct of emergency research through a system of oversight that integrates characteristics of quality improvement and health services research. PMID:25441519

  2. Randomized Controlled Trials in Environmental Health Research: Ethical Issues

    PubMed Central

    Resnik, David B.

    2009-01-01

    Background Randomized controlled trials (RCTs) are becoming increasingly common in environmental health research. Like all studies involving human subjects, environmental health RCTs raise many different ethical issues, ranging from obtaining informed consent, to minimizing risks, to protecting privacy and confidentiality. One of the most important issues raised by these studies is whether it is ethical to withhold effective environmental health interventions from research subjects in order to satisfy scientific objectives. Although environmental health investigators usually do not have professional obligations to provide medical care to research subjects, they have ethical obligations to avoid exploiting them. Withholding interventions from research subjects can be ethical, provided that it does not lead to exploitation of individuals or groups. To avoid exploiting individuals or groups, investigators should ensure that research subjects and study populations receive a fair share of the benefits of research. PMID:18236934

  3. Properties of permuted-block randomization in clinical trials.

    PubMed

    Matts, J P; Lachin, J M

    1988-12-01

    This article describes some of the important statistical properties of the commonly used permuted-block design, also known simply as blocked-randomization. Under a permutation model for statistical tests, proper analyses should employ tests that incorporate the blocking used in the randomization. These include the block-stratified Mantel-Haenszel chi-square test for binary data, the blocked analysis of variance F test, and the blocked nonparametric linear rank test. It is common, however, to ignore the blocking in the analysis. For these tests, it is shown that the size of a test obtained from an analysis incorporating the blocking (say T), versus an analysis ignoring the blocking (say TI), is related to the intrablock correlation coefficient (R) as TI = T(1-R). For blocks of common length 2m, the range of R is from -1/(2m-1) to 1. Thus, if there is a positive intrablock correlation, which is more likely than not for m greater than 1, an analysis ignoring blocking will be unduly conservative. Permutation tests are also presented for the case of stratified analyses within one or more subgroups of patients defined post hoc on the basis of a covariate. This provides a basis for the analysis when responses from some patients are assumed to be missing-at-random. An alternative strategy that requires no assumptions is to perform the analysis using only the subset of complete blocks in which no observations are missing. The Blackwell-Hodges model is used to assess the potential for selection bias induced by investigator attempts to guess which treatment is more likely to be assigned to each incoming patient. In an unmasked trial, the permuted-block design provides substantial potential for selection bias in the comparison of treatments due to the predictability of the assignments that is induced by the requirement of balance within blocks. Further, this bias is not eliminated by the use of random block sizes. We also modify the Blackwell-Hodges model to allow for

  4. Computerized Tool to Manage Dental Anxiety: A Randomized Clinical Trial.

    PubMed

    Tellez, M; Potter, C M; Kinner, D G; Jensen, D; Waldron, E; Heimberg, R G; Myers Virtue, S; Zhao, H; Ismail, A I

    2015-09-01

    Anxiety regarding dental and physical health is a common and potentially distressing problem, for both patients and health care providers. Anxiety has been identified as a barrier to regular dental visits and as an important target for enhancement of oral health-related quality of life. The study aimed to develop and evaluate a computerized cognitive-behavioral therapy dental anxiety intervention that could be easily implemented in dental health care settings. A cognitive-behavioral protocol based on psychoeducation, exposure to feared dental procedures, and cognitive restructuring was developed. A randomized controlled trial was conducted (N = 151) to test its efficacy. Consenting adult dental patients who met inclusion criteria (e.g., high dental anxiety) were randomized to 1 of 2 groups: immediate treatment (n = 74) or a wait-list control (n = 77). Analyses of covariance based on intention-to-treat analyses were used to compare the 2 groups on dental anxiety, fear, avoidance, and overall severity of dental phobia. Baseline scores on these outcomes were entered into the analyses as covariates. Groups were equivalent at baseline but differed at 1-mo follow-up. Both groups showed improvement in outcomes, but analyses of covariance demonstrated significant differences in dental anxiety, fear, avoidance, and overall severity of dental phobia in favor of immediate treatment at the follow-up assessment. Of the patients who met diagnostic criteria for phobia at baseline, fewer patients in the immediate treatment group continued to meet criteria for dental phobia at follow-up as compared with the wait-list group. A new computer-based tool seems to be efficacious in reducing dental anxiety and fear/avoidance of dental procedures. Examination of its effectiveness when administered in dental offices under less controlled conditions is warranted (ClinicalTrials.gov NCT02081365). PMID:26202996

  5. A randomized controlled trial of qigong for fibromyalgia

    PubMed Central

    2012-01-01

    Introduction Fibromyalgia is difficult to treat and requires the use of multiple approaches. This study is a randomized controlled trial of qigong compared with a wait-list control group in fibromyalgia. Methods One hundred participants were randomly assigned to immediate or delayed practice groups, with the delayed group receiving training at the end of the control period. Qigong training (level 1 Chaoyi Fanhuan Qigong, CFQ), given over three half-days, was followed by weekly review/practice sessions for eight weeks; participants were also asked to practice at home for 45 to 60 minutes per day for this interval. Outcomes were pain, impact, sleep, physical function and mental function, and these were recorded at baseline, eight weeks, four months and six months. Immediate and delayed practice groups were analyzed individually compared to the control group, and as a combination group. Results In both the immediate and delayed treatment groups, CFQ demonstrated significant improvements in pain, impact, sleep, physical function and mental function when compared to the wait-list/usual care control group at eight weeks, with benefits extending beyond this time. Analysis of combined data indicated significant changes for all measures at all times for six months, with only one exception. Post-hoc analysis based on self-reported practice times indicated greater benefit with the per protocol group compared to minimal practice. Conclusions This study demonstrates that CFQ, a particular form of qigong, provides long-term benefits in several core domains in fibromyalgia. CFQ may be a useful adjuvant self-care treatment for fibromyalgia. Trial registration clinicaltrials.gov NCT00938834. PMID:22863206

  6. Improving Osteoporosis Screening: Results from a Randomized Cluster Trial

    PubMed Central

    Kolk, Deneil; Peterson, Edward L.; McCarthy, Bruce D.; Weiss, Thomas W.; Chen, Ya-Ting; Muma, Bruce K.

    2007-01-01

    Background Despite recommendations, osteoporosis screening rates among women aged 65 years and older remain low. We present results from a clustered, randomized trial evaluating patient mailed reminders, alone and in combination with physician prompts, to improve osteoporosis screening and treatment. Methods Primary care clinics (n = 15) were randomized to usual care, mailed reminders alone, or mailed reminders with physician prompts. Study patients were females aged 65–89 years (N = 10,354). Using automated clinical and pharmacy data, information was collected on bone mineral density testing, pharmacy dispensings, and other patient characteristics. Unadjusted/adjusted differences in testing and treatment were assessed using generalized estimating equation approaches. Results Osteoporosis screening rates were 10.8% in usual care, 24.1% in mailed reminder, and 28.9% in mailed reminder with physician prompt. Results adjusted for differences at baseline indicated that mailed reminders significantly improved testing rates compared to usual care, and that the addition of prompts further improved testing. This effect increased with patient age. Treatment rates were 5.2% in usual care, 8.4% in mailed reminders, and 9.1% in mailed reminders with prompt. No significant differences were found in treatment rates between those receiving mailed reminders alone or in combination with physician prompts. However, women receiving usual care were significantly less likely to be treated. Conclusions The use of mailed reminders, either alone or with physician prompts, can significantly improve osteoporosis screening and treatment rates among insured primary care patients (Clinical Trials.gov number NCT00139425). PMID:17356966

  7. New treatments compared to established treatments in randomized trials

    PubMed Central

    Djulbegovic, Benjamin; Kumar, Ambuj; Glasziou, Paul P; Perera, Rafael; Reljic, Tea; Dent, Louise; Raftery, James; Johansen, Marit; Di Tanna, Gian Luca; Miladinovic, Branko; Soares, Heloisa P; Vist, Gunn E; Chalmers, Iain

    2012-01-01

    Background The proportion of proposed new treatments that are ’successful’ is of ethical, scientific, and public importance. We investigated how often new, experimental treatments evaluated in randomized controlled trials (RCTs) are superior to established treatments. Objectives Our main question was: “On average how often are new treatments more effective, equally effective or less effective than established treatments?” Additionally, we wanted to explain the observed results, i.e. whether the observed distribution of outcomes is consistent with the ’uncertainty requirement’ for enrollment in RCTs. We also investigated the effect of choice of comparator (active versus no treatment/placebo) on the observed results. Search methods We searched the Cochrane Methodology Register (CMR) 2010, Issue 1 in The Cochrane Library (searched 31 March 2010); MEDLINE Ovid 1950 to March Week 2 2010 (searched 24 March 2010); and EMBASE Ovid 1980 to 2010 Week 11 (searched 24 March 2010). Selection criteria Cohorts of studies were eligible for the analysis if they met all of the following criteria: (i) consecutive series of RCTs, (ii) registered at or before study onset, and (iii) compared new against established treatments in humans. Data collection and analysis RCTs from four cohorts of RCTs met all inclusion criteria and provided data from 743 RCTs involving 297,744 patients. All four cohorts consisted of publicly funded trials. Two cohorts involved evaluations of new treatments in cancer, one in neurological disorders, and one for mixed types of diseases. We employed kernel density estimation, meta-analysis and meta-regression to assess the probability of new treatments being superior to established treatments in their effect on primary outcomes and overall survival. Main results The distribution of effects seen was generally symmetrical in the size of difference between new versus established treatments. Meta-analytic pooling indicated that, on average, new treatments

  8. Dialysis fistula or graft: the role for randomized clinical trials.

    PubMed

    Allon, Michael; Lok, Charmaine E

    2010-12-01

    The Fistula First Initiative has strongly encouraged nephrologists, vascular access surgeons, and dialysis units in the United States to make valiant efforts to increase fistula use in the hemodialysis population. Unfortunately, the rigid "fistula first" recommendations are not based on solid, current, evidence-based data and may be harmful to some hemodialysis patients by subjecting them to prolonged catheter dependence with its attendant risks of bacteremia and central vein stenosis. Once they are successfully cannulated for dialysis, fistulas last longer than grafts and require fewer interventions to maintain long-term patency for dialysis. However, fistulas have a much higher primary failure rate than grafts, require more interventions to achieve maturation, and entail longer catheter dependence, thereby leading to more catheter-related complications. Given the tradeoffs between fistulas and grafts, there is equipoise about their relative merits in patients with moderate to high risk of fistula nonmaturation. The time is right for definitive, large, multicenter randomized clinical trials to compare fistulas and grafts in various subsets of chronic kidney disease patients. Until the results of such clinical trials are known, the optimal vascular access for a given patients should be determined by the nephrologist and access surgeon by taking into account (1) whether dialysis has been initiated, (2) the patient's life expectancy, (3) whether the patient has had a previous failed vascular access, and (4) the likelihood of fistula nonmaturation. Careful clinical judgment should optimize vascular access outcomes and minimize prolonged catheter dependence among hemodialysis patients. PMID:21030576

  9. A 3-year randomized therapeutic trial of nitisinone in alkaptonuria.

    PubMed

    Introne, Wendy J; Perry, Monique B; Troendle, James; Tsilou, Ekaterini; Kayser, Michael A; Suwannarat, Pim; O'Brien, Kevin E; Bryant, Joy; Sachdev, Vandana; Reynolds, James C; Moylan, Elizabeth; Bernardini, Isa; Gahl, William A

    2011-08-01

    Alkaptonuria is a rare, autosomal recessive disorder of tyrosine degradation due to deficiency of the third enzyme in the catabolic pathway. As a result, homogentisic acid (HGA) accumulates and is excreted in gram quantities in the urine, which turns dark upon alkalization. The first symptoms, occurring in early adulthood, involve a painful, progressively debilitating arthritis of the spine and large joints. Cardiac valvular disease and renal and prostate stones occur later. Previously suggested therapies have failed to show benefit, and management remains symptomatic. Nitisinone, a potent inhibitor of the second enzyme in the tyrosine catabolic pathway, is considered a potential therapy; proof-of-principle studies showed 95% reduction in urinary HGA. Based on those findings, a prospective, randomized clinical trial was initiated in 2005 to evaluate 40 patients over a 36-month period. The primary outcome parameter was hip total range of motion with measures of musculoskeletal function serving as secondary parameters. Biochemically, this study consistently demonstrated 95% reduction of HGA in urine and plasma over the course of 3 years. Clinically, primary and secondary parameters did not prove benefit from the medication. Side effects were infrequent. This trial illustrates the remarkable tolerability of nitisinone, its biochemical efficacy, and the need to investigate its use in younger individuals prior to development of debilitating arthritis. PMID:21620748

  10. The HAART cell phone adherence trial (WelTel Kenya1): a randomized controlled trial protocol

    PubMed Central

    Lester, Richard T; Mills, Edward J; Kariri, Antony; Ritvo, Paul; Chung, Michael; Jack, William; Habyarimana, James; Karanja, Sarah; Barasa, Samson; Nguti, Rosemary; Estambale, Benson; Ngugi, Elizabeth; Ball, T Blake; Thabane, Lehana; Kimani, Joshua; Gelmon, Lawrence; Ackers, Marta; Plummer, Francis A

    2009-01-01

    Background The objectives are to compare the effectiveness of cell phone-supported SMS messaging to standard care on adherence, quality of life, retention, and mortality in a population receiving antiretroviral therapy (ART) in Nairobi, Kenya. Methods and Design A multi-site randomized controlled open-label trial. A central randomization centre provided opaque envelopes to allocate treatments. Patients initiating ART at three comprehensive care clinics in Kenya will be randomized to receive either a structured weekly SMS ('short message system' or text message) slogan (the intervention) or current standard of care support mechanisms alone (the control). Our hypothesis is that using a structured mobile phone protocol to keep in touch with patients will improve adherence to ART and other patient outcomes. Participants are evaluated at baseline, and then at six and twelve months after initiating ART. The care providers keep a weekly study log of all phone based communications with study participants. Primary outcomes are self-reported adherence to ART and suppression of HIV viral load at twelve months scheduled follow-up. Secondary outcomes are improvements in health, quality of life, social and economic factors, and retention on ART. Primary analysis is by 'intention-to-treat'. Sensitivity analysis will be used to assess per-protocol effects. Analysis of covariates will be undertaken to determine factors that contribute or deter from expected and determined outcomes. Discussion This study protocol tests whether a novel structured mobile phone intervention can positively contribute to ART management in a resource-limited setting. Trial Registration Trial Registration Number: NCT00830622 PMID:19772596

  11. Postoperative pain relief following hysterectomy: A randomized controlled trial

    PubMed Central

    Raghvendra, K. P.; Thapa, Deepak; Mitra, Sukanya; Ahuja, Vanita; Gombar, Satinder; Huria, Anju

    2016-01-01

    Background: Women experience moderate to severe postoperative pain following total abdominal hysterectomy (TAH). The transversus abdominis plane (TAP) block is a new modality for providing postoperative pain relief in these patients. Materials and Methods: The present study was a single center, prospective randomized trial. After the Institutional Ethics Committee approval and informed consent, patients were randomized to either epidural group: Epidural block placement + general anesthesia (GA) or TAP group: Single shot TAP block + GA. Patients in both the groups received standard general anesthetic technique and intravenous tramadol patient-controlled analgesia in the postoperative period. Patients were monitored for tramadol consumption, visual analog scale (VAS) both at rest and on coughing, hemodynamics, and side effects at 0, 2, 4, 6, 8, 12, and 24 h postoperatively. Results: The total consumption of tramadol in 24 h was greater in TAP group as compared to epidural group (68.8 [25.5] vs. 5.3 [11.6] mg, P < 0.001). The VAS scores at rest and on coughing were higher in TAP group as compared to the epidural group at 6, 8, 12, and 24 h postoperatively (P < 0.05). None of the patients in either group had any adverse effects. Conclusion: Epidural analgesia provided greater tramadol-sparing effect with superior analgesia postoperatively as compared to TAP block in patients up to 24 h following TAH. PMID:27499592

  12. Enhancing antiepileptic drug adherence: a randomized controlled trial.

    PubMed

    Brown, Ian; Sheeran, Paschal; Reuber, Markus

    2009-12-01

    Suboptimal adherence to antiepileptic drug (AED) treatment is commonplace, and increases the risk of status epilepticus and sudden unexplained death in epilepsy. This randomized controlled trial was designed to demonstrate whether an implementation intention intervention involving the completion of a simple self-administered questionnaire linking the intention of taking medication with a particular time, place, and other activity can improve AED treatment schedule adherence. Of the 81 patients with epilepsy who were randomized, 69 completed a 1-month monitoring period with an objective measure of tablet taking (electronic registration of pill bottle openings, Medication Event Monitoring System [MEMS]). Intervention participants showed improved adherence relative to controls on all three outcomes: doses taken in total (93.4% vs. 79.1%), days on which correct dose was taken (88.7% vs. 65.3%), and doses taken on schedule (78.8% vs. 55.3%) (P<0.01). The implementation intention intervention may be an easy-to-administer and effective means of promoting AED adherence. PMID:19864187

  13. The Effectiveness of Propolis on Gingivitis: A Randomized Controlled Trial

    PubMed Central

    Paulino, Niraldo; Nör, Jacques E.; Moreira, Alexandre

    2014-01-01

    Abstract Background: A randomized, double-blind, controlled clinical trial was conducted to evaluate the effectiveness of a propolis rinse on induced gingivitis by using the co-twin study design. Methods: Twenty-one twin pairs (n=42) were enrolled in a gingivitis study with oral hygiene promotion (14 days) and gingivitis induction (21 days). During the gingivitis induction phase, one member of the twin pair was randomly assigned to a 2% typified propolis rinse, and the other was assigned a color-matched 0.05% sodium fluoride plus 0.05% cetylpyridinium chloride rinse (positive control). Patients rinsed twice daily with 20 mL for 30 seconds for 21 days. Gingivitis was measured on days −14 (baseline), 0 (after hygiene phase), and 21 (after no-hygiene phase) by using the Papillary Bleeding Score (PBS) and by standard digital imaging of the gum tissues (G-parameter). Results: The 38 persons who completed the study (age 13–22 years) were well balanced according to PBS at baseline and G-parameter after the initial hygiene phase. After 21 days without oral hygiene, the propolis rinse and positive control rinse groups did not differ significantly for average PBS measurements or G-parameter. Conclusions: Use of a 2% typified propolis rinse was equivalent to a positive control rinse during a 21-day no-hygiene period. PMID:25380344

  14. Treatment of bulimia nervosa with sertraline: a randomized controlled trial.

    PubMed

    Milano, W; Petrella, C; Sabatino, C; Capasso, A

    2004-01-01

    Bulimia nervosa (BN) is one of the most frequently encountered eating disorders in industrialized societies. It has been suggested that reduced serotonin activity may trigger some of the cognitive and mood disturbances associated with BN. Thus, pharmacologic treatment of BN is mainly based on the use of selective serotonin reuptake inhibitors, which have proved effective. At present, the biological basis of this disorder is not completely clear. The aim of this randomized, controlled trial was to verify the efficacy of sertraline, a selective serotonin reuptake inhibitor, in a group of patients with a diagnosis of BN. Twenty female outpatients, with an age range of 24 to 36 years and a diagnosis of purging type BN as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV), were assigned randomly to two treatment groups. The first group received sertraline 100 mg/day for 12 weeks; the second group received placebo. The study was conducted for 12 weeks, with weekly clinical assessments. At the end of the observation period, the group treated with sertraline had a statistically significant reduction in the number of binge eating crises and purging compared with the group who received placebo. In no case was treatment interrupted because of side effects. This study confirms that sertraline is well tolerated and effective in reducing binge-eating crises and purging in patients with BN. PMID:15605617

  15. Treatment of bulimia nervosa with fluvoxamine: a randomized controlled trial.

    PubMed

    Milano, W; Siano, C; Putrella, C; Capasso, A

    2005-01-01

    Bulimia nervosa (BN) is one of the most common eating disorders in industrialized societies. It has been suggested that reduced serotonin activity triggers some of the cognitive and mood disturbances associated with BN. For this reason, the pharmacologic treatment of BN consists mainly of selective serotonin reuptake inhibitors (SSRIs), which have been proven effective. At present, the physiologic bases of this disorder are not yet completely understood. We conducted a randomized controlled trial to verify the efficacy of the SSRI fluvoxamine in patients with a diagnosis of BN. Twelve female outpatients aged 21 to 34 years with a diagnosis of BN-binge purging (as defined by the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders [DSM IV]) were randomly assigned to 2 treatment groups: the fluvoxamine 200 mg/day group and the placebo group. The patients underwent weekly clinical assessments for 12 weeks. At the end of the observation period, there was a statistically significant reduction in the number of binge-eating crises and purging episodes in the fluvoxamine group compared with placebo. In no case was treatment interrupted because of emergent side effects. These findings support the hypothesis that fluvoxamine is well tolerated and effective in reducing binge-eating crises and purging episodes in patients with BN. PMID:16236688

  16. Surgical trial in traumatic intracerebral hemorrhage (STITCH(Trauma)): study protocol for a randomized controlled trial

    PubMed Central

    2012-01-01

    Background Intracranial hemorrhage occurs in over 60% of severe head injuries in one of three types: extradural (EDH); subdural (SDH); and intraparenchymal (TICH). Prompt surgical removal of significant SDH and EDH is established and widely accepted. However, TICH is more common and is found in more than 40% of severe head injuries. It is associated with a worse outcome but the role for surgical removal remains undefined. Surgical practice in the treatment of TICHs differs widely around the world. The aim of early surgery in TICH removal is to prevent secondary brain injury. There have been trials of surgery for spontaneous ICH (including the STICH II trial), but none so far of surgery for TICH. Methods/Design The UK National Institutes of Health Research has funded STITCH(Trauma) to determine whether a policy of early surgery in patients with TICH improves outcome compared to a policy of initial conservative treatment. It will include a health economics component and carry out a subgroup analysis of patients undergoing invasive monitoring. This is an international multicenter pragmatic randomized controlled trial. Patients are eligible if: they are within 48 h of injury; they have evidence of TICH on CT scan with a confluent volume of attenuation significantly raised above that of the background white and grey matter that has a total volume >10 mL; and their treating neurosurgeon is in equipoise. Patients will be ineligible if they have: a significant surface hematoma (EDH or SDH) requiring surgery; a hemorrhage/contusion located in the cerebellum; three or more separate hematomas fulfilling inclusion criteria; or severe pre-existing physical or mental disability or severe co-morbidity which would lead to poor outcome even if the patient made a full recovery from the head injury. Patients will be randomized via an independent service. Patients randomized to surgery receive surgery within 12 h. Both groups will be monitored according to standard neurosurgical

  17. Naturopathic Care for Anxiety: A Randomized Controlled Trial ISRCTN78958974

    PubMed Central

    Cooley, Kieran; Szczurko, Orest; Perri, Dan; Mills, Edward J.; Bernhardt, Bob; Zhou, Qi; Seely, Dugald

    2009-01-01

    Background Anxiety is a serious personal health condition and represents a substantial burden to overall quality of life. Additionally anxiety disorders represent a significant cost to the health care system as well as employers through benefits coverage and days missed due to incapacity. This study sought to explore the effectiveness of naturopathic care on anxiety symptoms using a randomized trial. Methods Employees with moderate to severe anxiety of longer than 6 weeks duration were randomized based on age and gender to receive naturopathic care (NC) (n = 41) or standardized psychotherapy intervention (PT) (n = 40) over a period of 12 weeks. Blinding of investigators and participants during randomization and allocation was maintained. Participants in the NC group received dietary counseling, deep breathing relaxation techniques, a standard multi-vitamin, and the herbal medicine, ashwagandha (Withania somnifera) (300 mg b.i.d. standardized to 1.5% withanolides, prepared from root). The PT intervention received psychotherapy, and matched deep breathing relaxation techniques, and placebo. The primary outcome measure was the Beck Anxiety Inventory (BAI) and secondary outcome measures included the Short Form 36 (SF-36), Fatigue Symptom Inventory (FSI), and Measure Yourself Medical Outcomes Profile (MY-MOP) to measure anxiety, mental health, and quality of life respectively. Participants were blinded to the placebo-controlled intervention. Results Seventy-five participants (93%) were followed for 8 or more weeks on the trial. Final BAI scores decreased by 56.5% (p<0.0001) in the NC group and 30.5% (p<0.0001) in the PT group. BAI group scores were significantly decreased in the NC group compared to PT group (p = 0.003). Significant differences between groups were also observed in mental health, concentration, fatigue, social functioning, vitality, and overall quality of life with the NC group exhibiting greater clinical benefit. No serious adverse reactions

  18. Prediction of Response to Treatment in a Randomized Clinical Trial of Couple Therapy: A 2-Year Follow-Up

    ERIC Educational Resources Information Center

    Baucom, Brian R.; Atkins, David C.; Simpson, Lorelei E.; Christensen, Andrew

    2009-01-01

    Many studies have examined pretreatment predictors of immediate posttreatment outcome, but few studies have examined prediction of long-term treatment response to couple therapies. Four groups of predictors (demographic, intrapersonal, communication, and other interpersonal) and 2 moderators (pretreatment severity and type of therapy) were…

  19. A Randomized, Pilot Trial of Etanercept in Dermatomyositis

    PubMed Central

    2011-01-01

    Objectives The aims of this pilot study were to assess (1) the safety and tolerability of etanercept in dermatomyositis (DM), (2) the feasibility and safety of a forced prednisone taper, and (3) outcome measures, including those recommended by the International Myositis Assessment Clinical Study Group (IMACS). Methods We conducted a randomized, double-blind, placebo-controlled trial of etanercept (50 mg SQ weekly) for 52 weeks in DM subjects. Subjects were tapered off prednisone in a standardized schedule as tolerated over the initial 24 weeks of the study. Principal outcomes included adverse events, time from randomization to treatment failure (inability to wean off prednisone on schedule), and average prednisone dosage after Week 24. Results Sixteen subjects were randomized, 11 to etanercept and 5 to placebo. There were no significant differences in adverse event rates between the treatment groups, although 5 etanercept-treated and 1 placebo-treated subjects developed worsening rash. All 5 subjects receiving placebo were treatment failures (median time to treatment failure 148 days). In contrast, 5/11 subjects in the etanercept arm were successfully weaned off prednisone; the median time to treatment failure in this group was 358 days (p = 0.0002). The median of the average prednisone dosage after Week 24 was 29.2 mg/day in the placebo group and 1.2 mg/day in the etanercept group (p = 0.02). IMACS and other outcome measures demonstrated excellent test-retest reliability (intraclass correlation coefficients 0.79 - 0.99). There was no significant treatment effect on functional outcome. Interpretation The observation of no major safety concerns and a steroid-sparing effect in our study suggest that further investigation of etanercept as a treatment for DM is warranted. PMID:21688301

  20. Efficacy of composite versus ceramic inlays and onlays: study protocol for the CECOIA randomized controlled trial

    PubMed Central

    2013-01-01

    Background Dental caries is a common disease and affects many adults worldwide. Inlay or onlay restoration is widely used to treat the resulting tooth substance loss. Two esthetic materials can be used to manufacture an inlay/onlay restoration of the tooth: ceramic or composite. Here, we present the protocol of a multicenter randomized controlled trial (RCT) comparing the clinical efficacy of both materials for tooth restoration. Other objectives are analysis of overall quality, wear, restoration survival and prognosis. Methods The CEramic and COmposite Inlays Assessment (CECOIA) trial is an open-label, parallel-group, multicenter RCT involving two hospitals and five private practices. In all, 400 patients will be included. Inclusion criteria are adults who need an inlay/onlay restoration for one tooth (that can be isolated with use of a dental dam and has at least one intact cusp), can tolerate restorative procedures and do not have severe bruxism, periodontal or carious disease or poor oral hygiene. The decayed tissue will be evicted, the cavity will be prepared for receiving an inlay/onlay and the patient will be randomized by use of a centralized web-based interface to receive: 1) a ceramic or 2) composite inlay or onlay. Treatment allocation will be balanced (1:1). The inlay/onlay will be adhesively luted. Follow-up will be for 2 years and may be extended; two independent examiners will perform the evaluations. The primary outcome measure will be the score obtained with use of the consensus instrument of the Fédération Dentaire Internationale (FDI) World Dental Federation. Secondary outcomes include this instrument’s items, inlay/onlay wear, overall quality and survival of the inlay/onlay. Data will be analyzed by a statistician blinded to treatments and an adjusted ordinal logistic regression model will be used to compare the efficacy of both materials. Discussion For clinicians, the CECOIA trial results may help with evidence-based recommendations

  1. Web-Based Mindfulness Intervention in Heart Disease: A Randomized Controlled Trial

    PubMed Central

    Younge, John O.; Wery, Machteld F.; Gotink, Rinske A.; Utens, Elisabeth M. W. J.; Michels, Michelle; Rizopoulos, Dimitris; van Rossum, Elisabeth F. C.

    2015-01-01

    Background Evidence is accumulating that mindfulness training has favorable effects on psychological outcomes, but studies on physiological outcomes are limited. Patients with heart disease have a high incidence of physiological and psychological problems and may benefit from mindfulness training. Our aim was to determine the beneficial physiological and psychological effects of online mindfulness training in patients with heart disease. Methods The study was a pragmatic randomized controlled single-blind trial. Between June 2012 and April 2014 we randomized 324 patients (mean age 43.2 years, 53.7% male) with heart disease in a 2:1 ratio (n = 215 versus n = 109) to a 12-week online mindfulness training in addition to usual care (UC) compared to UC alone. The primary outcome was exercise capacity measured with the 6 minute walk test (6MWT). Secondary outcomes were other physiological parameters (heart rate, blood pressure, respiratory rate, and NT-proBNP), subjective health status (SF-36), perceived stress (PSS), psychological well-being (HADS), social support (PSSS12) and a composite endpoint (all-cause mortality, heart failure, symptomatic arrhythmia, cardiac surgery, and percutaneous cardiac intervention). Linear mixed models were used to evaluate differences between groups on the repeated outcome measures. Results Compared to UC, mindfulness showed a borderline significant improved 6MWT (effect size, meters: 13.2, 95%CI: -0.02; 26.4, p = 0.050). There was also a significant lower heart rate in favor of the mindfulness group (effect size, beats per minute: -2.8, 95%CI: -5.4;-0.2, p = 0.033). No significant differences were seen on other outcomes. Conclusions Mindfulness training showed positive effects on the physiological parameters exercise capacity and heart rate and it might therefore be a useful adjunct to current clinical therapy in patients with heart disease. Trial Registration Dutch Trial Register 3453 PMID:26641099

  2. Surgical trials and trial registers: a cross-sectional study of randomized controlled trials published in journals requiring trial registration in the author instructions

    PubMed Central

    2013-01-01

    Background Trial registration and the reporting of trial results are essential to increase transparency in clinical research. Although both have been strongly promoted in recent years, it remains unclear whether they have been successfully implemented in surgery and surgery-related disciplines. In this cross-sectional study, we assessed whether randomized controlled trials (RCTs) published in surgery journals requiring trial registration in their author instructions were indeed registered, and whether the study results of registered RCTs had been submitted to the trial register and were thus publicly available. Methods The ten highest ranked surgery journals requiring trial registration by impact factor (Journal Citation Reports, JCR, 2011) were chosen. We then searched MEDLINE (in PubMed) for RCTs published in the selected journals between 1 June 2012 and 31 December 2012. Any trials recruiting participants before 2004 were excluded because the International Committee of Medical Journal Editors (ICMJE) first proposed trial registration in 2004. We then searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) to assess whether the identified RCTs were indeed registered and whether the results of the registered RCTs were available in the register. Results The search retrieved 588 citations. Four hundred and sixty references were excluded in the first screening. A further 25 were excluded after full-text screening. A total of 103 RCTs were finally included. Eighty-five of these RCTs (83%) could be found via the ICTRP. For 7 of 59 (12%) RCTs, which were registered on ClinicalTrials.gov, summary study data had been posted in the results database. Conclusions Although still not fully implemented, trial registration in surgery has gained momentum. In general, however, the submission of summary study data to ClinicalTrials.gov remains poor. PMID:24289719

  3. AIDS Clinical Trials Group Longitudinal Linked Randomized Trials (ALLRT): Rationale, Design, and Baseline Characteristics

    PubMed Central

    Smurzynski, Marlene; Collier, Ann C.; Koletar, Susan L.; Bosch, Ronald J.; Wu, Kunling; Bastow, Barbara; Benson, Constance A.

    2009-01-01

    Purpose ALLRT is a longitudinal cohort study of HIV-infected subjects prospectively randomized into selected clinical trials for antiretroviral (ARV) treatment-naïve and ARV treatment-experienced individuals conducted by the AIDS Clinical Trials Group (ACTG). We describe the rationale, design, and baseline characteristics of the ALLRT cohort and its potential to address important research questions related to ARV therapy. Method Standardized visits occur every 16 weeks to evaluate long-term clinical, virologic, and immunologic outcomes associated with ARV treatment. Results A total of 4,371 subjects enrolled in ALLRT from January 2000 through June 2007. Of these, 3,146 (72%) were ARV naïve at parent study entry (18% female, 44% white, 32% black, 21% Hispanic; median age 37 years, CD4 count 218 cells/μL, follow-up 3.6 years; 343 [11%] followed ≥8 years) and 1,225 (28%) were treatment experienced (13% female, 59% white, 20% black, 17% Hispanic; median age 42 years, CD4 count 325 cells/μL, follow-up 5.7 years). Conclusions ALLRT provides the opportunity to understand long-term ramifications of therapeutic ARV choices and determine whether these vary by treatment regimen, timing of treatment initiation, or treatment changes over long-term follow-up. Investigations based on uniform data and specimen collection in the context of randomized ARV treatments will be critical to developing more successful long-term therapeutic strategies for HIV treatment. PMID:18753121

  4. Impact of baseline anti-cyclic citrullinated peptide-2 antibody concentration on efficacy outcomes following treatment with subcutaneous abatacept or adalimumab: 2-year results from the AMPLE trial

    PubMed Central

    Sokolove, Jeremy; Schiff, Michael; Fleischmann, Roy; Weinblatt, Michael E; Connolly, Sean E; Johnsen, Alyssa; Zhu, Jin; Maldonado, Michael A; Patel, Salil; Robinson, William H

    2016-01-01

    Objectives To examine whether baseline anti-cyclic citrullinated peptide-2 (CCP2) antibody status and concentration correlated with clinical outcomes in patients treated with abatacept or adalimumab on background methotrexate (MTX) in the 2-year AMPLE (Abatacept versus adaliMumab comParison in bioLogic-naïvE rheumatoid arthritis subjects with background MTX) study. Methods In this exploratory analysis, anti-CCP2 antibody concentration was measured at baseline, and antibody-positive patients were divided into equal quartiles, Q1–Q4, representing increasing antibody concentrations. Clinical outcomes analysed by baseline anti-CCP2 status and quartile included change from baseline in disease activity and disability and remission rates. Results Baseline characteristics were generally comparable across quartiles and treatment groups. In both treatment groups, anti-CCP2 antibody-negative patients responded less well than antibody-positive patients. At year 2, improvements in disease activity and disability and remission rates were similar across Q1–Q3, but were numerically higher in Q4 in the abatacept group; in contrast, treatment effects were similar across all quartiles in the adalimumab group. Conclusions In AMPLE, baseline anti-CCP2 positivity was associated with a better response for abatacept and adalimumab. Patients with the highest baseline anti-CCP2 antibody concentrations had better clinical response with abatacept than patients with lower concentrations, an association that was not observed with adalimumab. Trial registration number NCT00929864. PMID:26359449

  5. A comparison of imputation strategies in cluster randomized trials with missing binary outcomes.

    PubMed

    Caille, Agnès; Leyrat, Clémence; Giraudeau, Bruno

    2014-04-01

    In cluster randomized trials, clusters of subjects are randomized rather than subjects themselves, and missing outcomes are a concern as in individual randomized trials. We assessed strategies for handling missing data when analysing cluster randomized trials with a binary outcome; strategies included complete case, adjusted complete case, and simple and multiple imputation approaches. We performed a simulation study to assess bias and coverage rate of the population-averaged intervention-effect estimate. Both multiple imputation with a random-effects logistic regression model or classical logistic regression provided unbiased estimates of the intervention effect. Both strategies also showed good coverage properties, even slightly better for multiple imputation with a random-effects logistic regression approach. Finally, this latter approach led to a slightly negatively biased intracluster correlation coefficient estimate but less than that with a classical logistic regression model strategy. We applied these strategies to a real trial randomizing households and comparing ivermectin and malathion to treat head lice. PMID:24713160

  6. Clarithromycin in GABA-related Hypersomnolence: A Randomized, Crossover Trial

    PubMed Central

    Trotti, Lynn Marie; Saini, Prabhjyot; Bliwise, Donald L.; Freeman, Amanda A.; Jenkins, Andrew; Rye, David B.

    2016-01-01

    Objective Some central hypersomnolence syndromes are associated with a positive allosteric modulator of GABA-A receptors in cerebrospinal fluid. Negative allosteric modulators of GABA-A receptors, including clarithromycin, have been reported to reduce sleepiness in these patients. We sought to systematically assess the effects of clarithromycin on objective vigilance and subjective sleepiness. Methods This was a five-week, randomized, placebo-controlled, double-blind, crossover trial of clarithromycin 500 mg with breakfast and lunch, in patients with hypersomnolence syndromes (excluding narcolepsy with cataplexy) and evidence for abnormal cerebrospinal fluid potentiation of GABA-A receptors. The study occurred at a university-affiliated medical center. The primary outcome measure was median reaction time on the psychomotor vigilance task (PVT) at week 2 in each condition. Secondary outcomes included the Epworth Sleepiness Scale, Stanford Sleepiness Scale, Functional Outcomes of Sleep, Pittsburgh Sleep Quality Index, the SF-36, and additional PVT measures. Results Twenty-three patients began treatment. Three patients dropped out, and final analyses were performed on twenty complete cases. Median reaction time was not significantly different between clarithromycin and placebo. Subjective measures of sleepiness were significantly improved on clarithromycin versus placebo. Altered taste perception occurred, but was the only side effect more common on clarithromycin than placebo. No serious adverse events occurred. Interpretation Subjective sleepiness, but not psychomotor vigilance, improved during a two-week course of clarithromycin. Although additional studies are needed, this suggests that clarithromycin may be a reasonable treatment option in patients with treatment-refractory hypersomnolence. This trial was registered at clinicaltrials.gov (NCT01146600) and supported by the American Sleep Medicine Foundation. PMID:26094838

  7. A Randomized Trial of Prenatal versus Postnatal Repair of Myelomeningocele

    PubMed Central

    Adzick, N. Scott; Thom, Elizabeth A.; Spong, Catherine Y.; Brock, John W.; Burrows, Pamela K.; Johnson, Mark P.; Howell, Lori J.; Farrell, Jody A.; Dabrowiak, Mary E.; Sutton, Leslie N.; Gupta, Nalin; Tulipan, Noel B.; D'Alton, Mary E.; Farmer, Diana L.

    2013-01-01

    Background Prenatal repair of myelomeningocele, the most common form of spina bifida, may result in better neurologic function than repair deferred until after delivery. We compared outcomes of in utero repair with standard postnatal repair. Methods We randomly assigned eligible women to undergo either prenatal surgery before 26 weeks of gestation or standard postnatal repair. One primary outcome was a composite of fetal or neonatal death or the need for placement of a cerebrospinal fluid shunt by the age of 12 months. Another primary outcome at 30 months was a composite of mental development and motor function. Results The trial was stopped for efficacy of prenatal surgery after the recruitment of 183 of a planned 200 patients. This report is based on results in 158 patients whose children were evaluated at 12 months. The first primary outcome occurred in 68% of the infants in the prenatal-surgery group and in 98% of those in the postnatal-surgery group (relative risk, 0.70; 97.7% confidence interval [CI], 0.58 to 0.84; P<0.001). Actual rates of shunt placement were 40% in the prenatal-surgery group and 82% in the postnatal-surgery group (relative risk, 0.48; 97.7% CI, 0.36 to 0.64; P<0.001). Prenatal surgery also resulted in improvement in the composite score for mental development and motor function at 30 months (P = 0.007) and in improvement in several secondary outcomes, including hindbrain herniation by 12 months and ambulation by 30 months. However, prenatal surgery was associated with an increased risk of preterm delivery and uterine dehiscence at delivery. Conclusions Prenatal surgery for myelomeningocele reduced the need for shunting and improved motor outcomes at 30 months but was associated with maternal and fetal risks. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00060606.) PMID:21306277

  8. Emphasized warning reduces salt intake: a randomized controlled trial.

    PubMed

    Pinjuh Markota, Nina; Rumboldt, Mirjana; Rumboldt, Zvonko

    2015-03-01

    Excessive salt intake is a major cardiovascular risk factor. At variance to the developed countries, the main source of sodium in transitional and developing countries is salt added while cooking and/or at the table. The objective of this trial was to examine the impact of warning labels placed on home salt containers on daily salt intake.A sample of treated hypertensives (n = 150) was randomized in two subgroups, one receiving just a leaflet about the harmful effects of excessive salt intake (control; n = 74), and the other one receiving in addition warning stickers for household salt containers (intervention; n = 76). Arterial blood pressure (BP) and 24-hour urinary sodium excretion (Na24) were measured in all the subjects at the start of the trial, and 1 month and 2 months later. The average starting Na24 was 207 ± 71 mmol in the control group and 211 ± 85 mmol in the intervention group (P = .745). One month and 2 months later, a significant decrease was observed in the intervention group (to 183 ± 63 mmol and 176 ± 55 mmol; P < .0001), as opposed to the control group (203 ± 60 mmol and 200 ± 58 mmol; P = .1466). Initial BP was 143.7/84.1 mm Hg in the control, and 142.9/84.7 mm Hg in the intervention group (P = .667). One month and 2 months later, a significant drop in BP, by 5.3/2.9 mm Hg, was observed in the intervention group as opposed to the control group (0.4/0.9 mm Hg). Decrease in Na24 positively correlated to BP lowering (r(2) = 0.5989; P < .0001). A significant reduction in 24Na and BP is achieved with warning labels on harmful effects of excessive salt intake. Decreasing daily salt input by 35 mmol may result in an extra BP lowering by some 5-6/2-3 mm Hg. PMID:25659228

  9. Prosthetic heart valves: Objective Performance Criteria versus randomized clinical trial.

    PubMed

    Grunkemeier, Gary L; Jin, Ruyun; Starr, Albert

    2006-09-01

    The current Food and Drug Administration (FDA) heart valve guidance document uses an objective performance criteria (OPC) methodology to evaluate the clinical performance of prosthetic heart valves. OPC are essentially historical controls, but they have turned out to be an adequate, and perhaps optimal, study design in this situation. Heart valves have a simple open-and-close mechanism, device effectiveness is easy to document, and the common complications (thromboembolism, thrombosis, bleeding, leak, and infection) are well known and easily detected. Thus, randomized clinical trials (RCTs) have not been deemed necessary for the regulatory approval of prosthetic heart valves. The OPC are derived from the average complication rates of all approved heart valves. Studies based on OPC have been shown to work well; many different valve models have gained FDA market approval based on this methodology. Although heart valve RCTs are not required by the FDA, they have been done to compare valves or treatment regimens after approval. Recently, the Artificial Valve Endocarditis Reduction Trial (AVERT) was designed to compare a new Silzone sewing ring, designed to reduce infection, with the Standard sewing ring on a St. Jude Medical heart valve. This was the largest heart valve RCT ever proposed (4,400 valve patients, followed for as long as 4 years), but it was stopped prematurely because of a high leak rate associated with the Silzone valve. Examining the results showed that a much smaller, OPC-based study with 800 patient-years would have been sufficient to disclose this complication of the Silzone valve. PMID:16928482

  10. Nicotine patch preloading for smoking cessation (the preloading trial): study protocol for a randomized controlled trial

    PubMed Central

    2014-01-01

    Background The use of nicotine replacement therapy before quitting smoking is called nicotine preloading. Standard smoking cessation protocols suggest commencing nicotine replacement therapy only on the first day of quitting smoking (quit day) aiming to reduce withdrawal symptoms and craving. However, other, more successful smoking cessation pharmacotherapies are used prior to the quit day as well as after. Nicotine preloading could improve quit rates by reducing satisfaction from smoking prior to quitting and breaking the association between smoking and reward. A systematic literature review suggests that evidence for the effectiveness of preloading is inconclusive and further trials are needed. Methods/Design This is a study protocol for a multicenter, non-blinded, randomized controlled trial based in the United Kingdom, enrolling 1786 smokers who want to quit, funded by the National Institute for Health Research, Health Technology Assessment program, and sponsored by the University of Oxford. Participants will primarily be recruited through general practices and smoking cessation clinics, and randomized (1:1) either to use 21 mg nicotine patches, or not, for four weeks before quitting, whilst smoking as normal. All participants will be referred to receive standard smoking cessation service support. Follow-ups will take place at one week, four weeks, six months and 12 months after quit day. The primary outcome will be prolonged, biochemically verified six-month abstinence. Additional outcomes will include point prevalence abstinence and abstinence of four-week and 12-month duration, side effects, costs of treatment, and markers of potential mediators and moderators of the preloading effect. Discussion This large trial will add substantially to evidence on the effectiveness of nicotine preloading, but also on its cost effectiveness and potential mediators, which have not been investigated in detail previously. A range of recruitment strategies have been

  11. A Randomized Trial Comparing Skin Antiseptic Agents at Cesarean Delivery

    PubMed Central

    Tuuli, Methodius G.; Liu, Jingxia; Stout, Molly J.; Martin, Shannon; Cahill, Alison G.; Odibo, Anthony O.; Colditz, Graham A.; Macones, George A.

    2016-01-01

    BACKGROUND Preoperative skin antisepsis has the potential to decrease the risk of surgical-site infection. However, evidence is limited to guide the choice of antiseptic agent at cesarean delivery, which is the most common major surgical procedure among women in the United States. METHODS In this single-center, randomized, controlled trial, we evaluated whether the use of chlorhexidine–alcohol for preoperative skin antisepsis was superior to the use of iodine–alcohol for the prevention of surgical-site infection after cesarean delivery. We randomly assigned patients undergoing cesarean delivery to skin preparation with either chlorhexidine–alcohol or iodine–alcohol. The primary outcome was superficial or deep surgical-site infection within 30 days after cesarean delivery, on the basis of definitions from the Centers for Disease Control and Prevention. RESULTS From September 2011 through June 2015, a total of 1147 patients were enrolled; 572 patients were assigned to chlorhexidine–alcohol and 575 to iodine–alcohol. In an intention-to-treat analysis, surgical-site infection was diagnosed in 23 patients (4.0%) in the chlorhexidine–alcohol group and in 42 (7.3%) in the iodine–alcohol group (relative risk, 0.55; 95% confidence interval, 0.34 to 0.90; P = 0.02). The rate of superficial surgical-site infection was 3.0% in the chlorhexidine–alcohol group and 4.9% in the iodine–alcohol group (P = 0.10); the rate of deep infection was 1.0% and 2.4%, respectively (P = 0.07). The frequency of adverse skin reactions was similar in the two groups. CONCLUSIONS The use of chlorhexidine–alcohol for preoperative skin antisepsis resulted in a significantly lower risk of surgical-site infection after cesarean delivery than did the use of iodine–alcohol. (Funded by the National Institutes of Health and Washington University School of Medicine in St. Louis; ClinicalTrials.gov number, NCT01472549.) PMID:26844840

  12. Comparing community and specialty provider-based recruitment in a randomized clinical trial: clinical trial in fecal incontinence

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recruitment of participants to clinical trials remains a significant challenge, especially for research addressing topics of a sensitive nature such as fecal incontinence (FI). The Fiber Study, a randomized controlled trial on symptom management for FI, successfully enrolled 189 community-living adu...

  13. A Randomized Controlled Trial of Storytelling as a Communication Tool

    PubMed Central

    Hartling, Lisa; Scott, Shannon D.; Johnson, David W.; Bishop, Ted; Klassen, Terry P.

    2013-01-01

    Introduction Stories may be an effective tool to communicate with patients because of their ability to engage the reader. Our objective was to evaluate the effectiveness of story booklets compared to standard information sheets for parents of children attending the emergency department (ED) with a child with croup. Methods Parents were randomized to receive story booklets (n=208) or standard information sheets (n=205) during their ED visit. The primary outcome was change in anxiety between triage to ED discharge as measured by the State-Trait Anxiety Inventory. Follow-up telephone interviews were conducted at 1 and 3 days after discharge, then every other day until 9 days (or until resolution of symptoms), and at 1 year. Secondary outcomes included: expected future anxiety, event impact, parental knowledge, satisfaction, decision regret, healthcare utilization, time to symptom resolution. Results There was no significant difference in the primary outcome of change in parental anxiety between recruitment and ED discharge (change of 5 points for the story group vs. 6 points for the comparison group, p=0.78). The story group showed significantly greater decision regret regarding their decision to go to the ED (p<0.001): 6.7% of the story group vs. 1.5% of the comparison group strongly disagreed with the statement “I would go for the same choice if I had to do it over again”. The story group reported shorter time to resolution of symptoms (mean 3.7 days story group vs. 4.0 days comparison group, median 3 days both groups; log rank test, p=0.04). No other outcomes were different between study groups. Conclusions Stories about parent experiences managing a child with croup did not reduce parental anxiety. The story group showed significantly greater decision regret and quicker time to resolution of symptoms. Further research is needed to better understand whether stories can be effective in improving patient-important outcomes. Trial Registration Current Controlled

  14. Key Items to Get Right When Conducting a Randomized Controlled Trial in Education

    ERIC Educational Resources Information Center

    Coalition for Evidence-Based Policy, 2005

    2005-01-01

    This is a checklist of key items to get right when conducting a randomized controlled trial to evaluate an educational program or practice ("intervention"). It is intended as a practical resource for researchers and sponsors of research, describing items that are often critical to the success of a randomized controlled trial. A significant…

  15. A Randomized Trial of Telephone Psychotherapy and Pharmacotherapy for Depression: Continuation and Durability of Effects

    ERIC Educational Resources Information Center

    Ludman, Evette J.; Simon, Gregory E.; Tutty, Steve; Von Korff, Michael

    2007-01-01

    Randomized trial evidence and expert guidelines are mixed regarding the value of combined pharmacotherapy and psychotherapy as initial treatment for depression. This study describes long-term results of a randomized trial (N = 393) evaluating telephone-based cognitive-behavioral therapy (CBT) plus care management for primary care patients…

  16. The Deckled Incision: Study Protocol for a Randomized Controlled Trial

    PubMed Central

    Lord, Sarah J; Ngo, Quan

    2016-01-01

    Background Scar visibility is multifactorial and skin closure technique is thought to play an important role. It is an established principle in plastic surgery that Z plasties generally reduce scar contracture by breaking up the lines of tension in a wound. As an extension of this principle, it is postulated that irregular “deckled” skin incisions made during tumor excision would produce aesthetically superior scars. Objective The primary objective of this study is to assess both the clinician and patient opinion of scar quality using the Patient and Observer Scar Assessment Scale (POSAS). Secondary objectives include the proportion of scars judged as good by the both the patient and clinician (less than or equal to 5 on the overall PSOAS scale), the number of adverse events, and the proportion of the scar visible at 1 meter. Methods The deckling study will be a patient-blinded, simple randomized controlled trial (RCT) at a single center institution. The two groups will be equally allocated on a 1:1 ratio into the control and treatment arms. All patients greater than 18 years of age undergoing a plastic surgery procedure involving excision of skin lesions will be enrolled. Any patients requiring re-excision through the wound or undergoing injectable corticosteroid therapy will be excluded. A total of 500 patients will be enrolled. The patients will be followed-up at 1 week, 3 months, and 6 months post-operatively. Results The study is expected to begin enrolment in August 2016. We anticipate that the deckling study group will have superior scar outcomes when compared to the straight line incision. From clinical experience this is especially true for lesions involving the face and in those areas of the skin that have undergone radiation therapy. The study will be funded by the Plastics and Reconstructive Surgery Department at St Vincent’s Hospital, Sydney, Australia. Ethics approval has been obtained for the study. Conclusion: We believe this will be an

  17. Rural providers' access to online resources: a randomized controlled trial

    PubMed Central

    Hall, Laura J.; McElfresh, Karen R.; Warner, Teddy D.; Stromberg, Tiffany L.; Trost, Jaren; Jelinek, Devin A.

    2016-01-01

    Objective The research determined the usage and satisfaction levels with one of two point-of-care (PoC) resources among health care providers in a rural state. Methods In this randomized controlled trial, twenty-eight health care providers in rural areas were stratified by occupation and region, then randomized into either the DynaMed or the AccessMedicine study arm. Study participants were physicians, physician assistants, and nurses. A pre- and post-study survey measured participants' attitudes toward different information resources and their information-seeking activities. Medical student investigators provided training and technical support for participants. Data analyses consisted of analysis of variance (ANOVA), paired t tests, and Cohen's d statistic to compare pre- and post-study effects sizes. Results Participants in both the DynaMed and the AccessMedicine arms of the study reported increased satisfaction with their respective PoC resource, as expected. Participants in both arms also reported that they saved time in finding needed information. At baseline, both arms reported too little information available, which increased to “about right amounts of information” at the completion of the study. DynaMed users reported a Cohen's d increase of +1.50 compared to AccessMedicine users' reported use of 0.82. DynaMed users reported d2 satisfaction increases of 9.48 versus AccessMedicine satisfaction increases of 0.59 using a Cohen's d. Conclusion Participants in the DynaMed arm of the study used this clinically oriented PoC more heavily than the users of the textbook-based AccessMedicine. In terms of user satisfaction, DynaMed users reported higher levels of satisfaction than the users of AccessMedicine. PMID:26807050

  18. Sildenafil for Chronic Obstructive Pulmonary Disease: A Randomized Crossover Trial

    PubMed Central

    Lederer, David J.; Bartels, Matthew N.; Schluger, Neil W.; Brogan, Frances; Jellen, Patricia; Thomashow, Byron M.; Kawut, Steven M.

    2016-01-01

    Rationale Pulmonary hypertension with exercise is common in chronic obstructive pulmonary disease (COPD) and may contribute to exercise limitation in this disease. We aimed to determine the effects of treatment with sildenafil on exercise capacity in patients with COPD and emphysema. Methods We performed a randomized, double-blind, placebo-controlled 2-period crossover trial of sildenafil thrice daily in ten adults with COPD and emphysema on CT scan without pulmonary hypertension. We randomized study participants to 4 weeks of sildenafil (or placebo) followed by a 1-week washout and then 4 weeks of placebo (or sildenafil). The 2 primary outcomes were the 6-minute walk distance and oxygen consumption at peak exercise. Results Sildenafil had no effect on 6-minute walk distance (placebo-corrected difference = −7.8 m, 95% confidence interval, −23.2 to 7.5 m, p = 0.35) or oxygen consumption at peak exercise (placebo-corrected difference = −0.1 ml/kg/min, 95% confidence interval −2.1 to 1.8 ml/kg/min, p = 0.89). Sildenafil increased the alveolar-arterial oxygen gradient (p = 0.02), worsened symptoms (p = 0.04), and decreased quality-of-life (p = 0.03). Adverse events were more frequent while receiving sildenafil (p = 0.005). Conclusions Routine sildenafil administration did not have a beneficial effect on exercise capacity in patients with COPD and emphysema without pulmonary hypertension. Sildenafil significantly worsened gas exchange at rest and quality of life. (clinicaltrials.gov NCT00104637). PMID:22360383

  19. Snoezelen Room and Childbirth Outcome: A Randomized Clinical Trial

    PubMed Central

    Jamshidi Manesh, Mansoureh; Kalati, Mahnaz; Hosseini, Fatemeh

    2015-01-01

    Background: One of the strategies for a good outcome and pain free childbearing is to design the delivery room. Objectives: The aim of this study was to evaluate the effects of snoezelen room on childbearing outcome such as pain intensity, duration of labor, and perinea status in nulliparous women. Patients and Methods: This study was a randomized controlled clinical trial consists of 100 childbearing women. They were randomly divided into 2 groups. The experimental group went to snoezelen room when their cervix dilation was 4 cm, while the control group went to physiologic delivery room with the same cervix dilation. Results: The mean ± SD of VAS (Visual Analogue Scale) pain intensity of the experimental and control groups before the intervention were 5.1 ± 1.95 and 5.58 ± 1.62, respectively (P = 0.13). The mean ± SD of VAS pain intensity scores of the experimental and control groups after 3 hours spending in their assigned rooms were 5.26 ± 0.86 and 9.56 ± 1.48, respectively (P = 0.01). The mean ± SD of the first stage scores of the experimental and control groups were 6.95 ± 0.97 and 8.41 ± 0.67, respectively (P = 0.042). About 92% of participants’ intervention vs. 66% of control participants had perinea laceration (P = 0.041). Conclusions: According to the findings of the present study, distracting senses in snoezelen room decreases mother’s pain intensity, the length of labor, and incidence of episiotomy. PMID:26082849

  20. Control of Blood Pressure and Risk Attenuation: Post Trial Follow-Up of Randomized Groups

    PubMed Central

    Jafar, Tazeen H.; Jehan, Imtiaz; Liang, Feng; Barbier, Sylvaine; Islam, Muhammad; Bux, Rasool; Khan, Aamir Hameed; Nadkarni, Nivedita; Poulter, Neil; Chaturvedi, Nish; Ebrahim, Shah

    2015-01-01

    Background Evidence on long term effectiveness of public health strategies for lowering blood pressure (BP) is scarce. In the Control of Blood Pressure and Risk Attenuation (COBRA) Trial, a 2 x 2 factorial, cluster randomized controlled trial, the combined home health education (HHE) and trained general practitioner (GP) intervention delivered over 2 years was more effective than no intervention (usual care) in lowering systolic BP among adults with hypertension in urban Pakistan. However, it was not clear whether the effect would be sustained after the cessation of intervention. We conducted 7 years follow-up inclusive of 5 years of post intervention period of COBRA trial participants to assess the effectiveness of the interventions on BP during extended follow-up. Methods A total of 1341 individuals 40 years or older with hypertension (systolic BP 140 mm Hg or greater, diastolic BP 90 mm Hg or greater, or already receiving treatment) were followed by trained research staff masked to randomization status. BP was measured thrice with a calibrated automated device (Omron HEM-737 IntelliSense) in the sitting position after 5 minutes of rest. BP measurements were repeated after two weeks. Generalized estimating equations (GEE) were used to analyze the primary outcome of change in systolic BP from baseline to 7- year follow-up. The multivariable model was adjusted for clustering, age at baseline, sex, baseline systolic and diastolic BP, and presence of diabetes. Findings After 7 years of follow-up, systolic BP levels among those randomised to combined HHE plus trained GP intervention were significantly lower (2.1 [4.1–0.1] mm Hg) compared to those randomised to usual care, (P = 0.04). Participants receiving the combined intervention compared to usual care had a greater reduction in LDL-cholesterol (2.7 [4.8 to 0.6] mg/dl. Conclusions The benefit in systolic BP reduction observed in the original cohort assigned to the combined intervention was attenuated but still

  1. Sexual assault resistance education for university women: study protocol for a randomized controlled trial (SARE trial)

    PubMed Central

    2013-01-01

    Background More than one in six women will be sexually assaulted in their lifetimes, most by men they know. The situation on university campuses is even more startling, with as many as 1 in 4 female students being victims of rape or attempted rape. The associated physical and mental health effects are extensive and the social and economic costs are staggering. The aim of this randomized controlled trial is to determine whether a novel, small-group sexual assault resistance education program can reduce the incidence of sexual assault among university-attending women, when compared to current university practice of providing informational brochures. Methods/Design The trial will evaluate a theoretically and empirically sound four-unit, 12-hour education program that has been demonstrated in pilot studies to have short-term efficacy. Three of the four units provide information, skills, and practice aimed at decreasing the time needed for women to assess situations with elevated risk of acquaintance sexual assault as dangerous and to take action, reducing emotional obstacles to taking action, and increasing the use of the most effective methods of verbal and physical self-defense. The fourth unit focuses on facilitating a stronger positive sexuality from which women may resist sexual coercion by male intimates more successfully. The trial will extend the pilot evaluations by expanding the participant pool and examining the long term efficacy of the program. A total of 1716 first-year female students (age 17 to 24 years) from three Canadian universities will be enrolled. The primary outcome is completed sexual assault, measured by The Sexual Experiences Survey - Short Form Victimization instrument. Secondary outcomes include changes in knowledge, attitudes, and skills related to the process of sexual assault resistance. Outcomes will be measured at baseline, 1 week, 6, 12, 18, and 24 months. Discussion The results of the trial will be used to produce a maximally

  2. Sublingual immunotherapy for peanut allergy: Long-term follow-up of a randomized multicenter trial

    PubMed Central

    Burks, A. Wesley; Wood, Robert A.; Jones, Stacie M.; Sicherer, Scott H.; Fleischer, David M.; Scurlock, Amy M.; Vickery, Brian P.; Liu, Andrew H.; Henning, Alice K.; Lindblad, Robert; Dawson, Peter; Plaut, Marshall; Sampson, Hugh A.

    2015-01-01

    Background We previously reported initial results of the first multi-center randomized, double blind, placebo controlled clinical trial of peanut sublingual immunotherapy (SLIT), observing a favorable safety profile associated with modest clinical and immunologic effects in the first year. Objective To provide long-term (3-year) clinical and immunologic outcomes for our peanut SLIT trial. Key endpoints: (1) percentage of responders at 2 years (could consume 5g of peanut powder or a 10-fold increase from baseline), 2) percentage reaching desensitization at 3 years, (3) percentage attaining sustained unresponsiveness after 3 years, (4) immunologic endpoints and (5) assessment of safety parameters. Methods Response to treatment was evaluated in 40 subjects aged 12-40 years by performing a 10g peanut powder oral food challenge (OFC) following 2 and 3 years of daily peanut SLIT therapy. At 3 years, SLIT was discontinued for 8 weeks followed by another 10g OFC, and an open feeding of peanut butter to assess sustained unresponsiveness. Results Approximately 98% of the 18,165 doses were tolerated without adverse reactions beyond the oropharynx, with no severe symptoms or uses of epinephrine. A high rate (>50%) discontinued therapy. By study end, 4/37 (10.8%) of SLIT treated participants were fully desensitized to 10g of peanut powder, and all 4 achieved sustained unresponsiveness. Responders at 2 years showed a significant decrease in peanut-specific basophil activation and skin prick test titration compared to non-responders. Conclusions Peanut SLIT induced a modest level of desensitization, decreased immunologic activity over 3 years in responders, and had an excellent long-term safety profile. However, most patients discontinued therapy by the end of year 3, and only 10.8% of subjects achieved sustained unresponsiveness. PMID:25656999

  3. Effects of nattokinase on blood pressure: a randomized, controlled trial.

    PubMed

    Kim, Ji Young; Gum, Si Nae; Paik, Jean Kyung; Lim, Hyo Hee; Kim, Kyong-Chol; Ogasawara, Kazuya; Inoue, Kenichi; Park, Sungha; Jang, Yangsoo; Lee, Jong Ho

    2008-08-01

    The objective of this study was to examine the effects of nattokinase supplementation on blood pressure in subjects with pre-hypertension or stage 1 hypertension. In a randomized, double-blind, placebo-controlled trial, 86 participants ranging from 20 to 80 years of age with an initial untreated systolic blood pressure (SBP) of 130 to 159 mmHg received nattokinase (2,000 FU/capsule) or a placebo capsule for 8 weeks. Seventy-three subjects completed the protocol. Compared with the control group, the net changes in SBP and diastolic blood pressure (DBP) were -5.55 mmHg (95% confidence interval [CI], -10.5 to -0.57 mmHg; p<0.05) and -2.84 mmHg (CI, -5.33 to -0.33 mmHg; p<0.05), respectively, after the 8-week intervention. The corresponding net change in renin activity was -1.17 ng/mL/h for the nattokinase group compared with the control group (p<0.05). In conclusion, nattokinase supplementation resulted in a reduction in SBP and DBP. These findings suggest that increased intake of nattokinase may play an important role in preventing and treating hypertension. PMID:18971533

  4. Randomized Trial of Clarithromycin for Mediterranean Spotted Fever.

    PubMed

    Anton, Esperança; Muñoz, Tomas; Travería, Francisco Javier; Navarro, Gemma; Font, Bernat; Sanfeliu, Isabel; Segura, Ferran

    2015-01-01

    The classic antibiotic treatment for Mediterranean spotted fever (MSF) is based on tetracyclines or chloramphenicol, but chloramphenicol's bone marrow toxicity makes tetracyclines the treatment of choice. However, it is convenient to have alternatives available for patients who are allergic to tetracyclines, pregnant women, and children <8 years old. We conducted a randomized clinical trial to compare clarithromycin with doxycycline or josamycin in the treatment of MSF. Forty patients were evaluated (23 male; mean age, 39.87 years); 13 patients were aged <14 years. Seventeen patients received clarithromycin, and 23 received doxycycline or josamycin. The interval between the onset of symptoms and the start of treatment was 4.04 ± 1.70 days in the clarithromycin group versus 4.11 ± 1.60 days in the doxycycline/josamycin group (P = not significant [NS]). Time to the disappearance of fever after treatment was 2.67 ± 1.55 days in the clarithromycin group versus 2.22 ± 1.35 days in the doxycycline/josamycin (P = NS). The symptoms had disappeared at 4.70 ± 2.25 days in the clarithromycin group versus at 4.75 ± 3.08 days in the doxycycline/josamycin (P = NS). There were no adverse reactions to treatment or relapses in either group. In conclusion, clarithromycin is a good alternative to doxycycline or josamycin in the treatment of MSF. PMID:26711765

  5. Acupuncture for posttraumatic stress disorder: a randomized controlled pilot trial.

    PubMed

    Hollifield, Michael; Sinclair-Lian, Nityamo; Warner, Teddy D; Hammerschlag, Richard

    2007-06-01

    The purpose of the study was to evaluate the potential efficacy and acceptability of accupuncture for posttraumatic stress disorder (PTSD). People diagnosed with PTSD were randomized to either an empirically developed accupuncture treatment (ACU), a group cognitive-behavioral therapy (CBT), or a wait-list control (WLC). The primary outcome measure was self-reported PTSD symptoms at baseline, end treatment, and 3-month follow-up. Repeated measures MANOVA was used to detect predicted Group X Time effects in both intent-to-treat (ITT) and treatment completion models. Compared with the WLC condition in the ITT model, accupuncture provided large treatment effects for PTSD (F [1, 46] = 12.60; p < 0.01; Cohen's d = 1.29), similar in magnitude to group CBT (F [1, 47] = 12.45; p < 0.01; d = 1.42) (ACU vs. CBT, d = 0.29). Symptom reductions at end treatment were maintained at 3-month follow-up for both interventions. Accupuncture may be an efficacious and acceptable nonexposure treatment option for PTSD. Larger trials with additional controls and methods are warranted to replicate and extend these findings. PMID:17568299

  6. Randomized clinical trial of topical tranexamic acid after reduction mammoplasty

    PubMed Central

    Ausen, K; Fossmark, R; Spigset, O; Pleym, H

    2015-01-01

    Background The antifibrinolytic drug tranexamic acid is currently being rediscovered for both trauma and major surgery. Intravenous administration reduces the need for blood transfusion and blood loss by about one-third, but routine administration in surgery is not yet advocated owing to concerns regarding thromboembolic events. The aim of this study was to investigate whether topical application of tranexamic acid to a wound surface reduces postoperative bleeding. Methods This was a randomized double-blind placebo-controlled trial on 30 consecutive women undergoing bilateral reduction mammoplasty. On one side the wound surfaces were moistened with 25 mg/ml tranexamic acid before closure, and placebo (saline) was used on the other side. Drain fluid production was measured for 24 h after surgery, and pain was measured after 3 and 24 h. Postoperative complications including infection, seroma, rebleeding and suture reactions were recorded. Results Topical application of tranexamic acid to the wound surface after reduction mammoplasty reduced drain fluid production by 39 per cent (median 12·5 (range 0–44) versus 20·5 (0–100) ml; P = 0·038). Adverse effects were not observed. There were no significant differences in postoperative pain scores or complications. Conclusion Topical application of dilute tranexamic acid reduced bleeding in this model. The study adds to the evidence that this simple procedure may reduce wound bleeding after surgery. Registration number: NCT01964781 (http://www.clinicaltrials.gov). PMID:26349843

  7. Ameliorating children's reading-comprehension difficulties: a randomized controlled trial.

    PubMed

    Clarke, Paula J; Snowling, Margaret J; Truelove, Emma; Hulme, Charles

    2010-08-01

    Children with specific reading-comprehension difficulties can read accurately, but they have poor comprehension. In a randomized controlled trial, we examined the efficacy of three interventions designed to improve such children's reading comprehension: text-comprehension (TC) training, oral-language (OL) training, and TC and OL training combined (COM). Children were assessed preintervention, midintervention, postintervention, and at an 11-month follow-up. All intervention groups made significant improvements in reading comprehension relative to an untreated control group. Although these gains were maintained at follow-up in the TC and COM groups, the OL group made greater gains than the other groups did between the end of the intervention and follow-up. The OL and COM groups also demonstrated significant improvements in expressive vocabulary compared with the control group, and this was a mediator of the improved reading comprehension of the OL and COM groups. We conclude that specific reading-comprehension difficulties reflect (at least partly) underlying oral-language weaknesses that can be effectively ameliorated by suitable teaching. PMID:20585051

  8. Comparison of olanzapine long-acting injection and oral olanzapine: a 2-year, randomized, open-label study in outpatients with schizophrenia.

    PubMed

    Detke, Holland C; Weiden, Peter J; Llorca, Pierre-Michel; Choukour, Moutaz; Watson, Susan B; Brunner, Elizabeth; Ascher-Svanum, Haya

    2014-08-01

    We compared long-term treatment effectiveness of monthly olanzapine long-acting injection (LAI) with that of oral olanzapine. Outpatients with 2 or more episodes of psychotic worsening in the past 24 months with Positive and Negative Syndrome Scale total score of lower than 70 were randomized to 405 mg/4 weeks of olanzapine LAI (n = 264) or 10 mg/d of oral olanzapine (n = 260) for 2 years of open-label treatment. Dosing thereafter was flexible (150-405 mg/4 weeks of LAI vs 5-20 mg/d of oral). Primary outcome was time to all-cause discontinuation. At baseline, patients were clinically stable (mean Positive and Negative Syndrome Scale total score of 57). Seventeen percent of patients had been psychiatrically hospitalized in the previous 6 months, and 4.6% were rated nonadherent in the month before study entry. The groups did not differ significantly in median time to all-cause discontinuation (645 days for LAI, 678 days for oral; P = 0.61), discontinuation rate (53.8% for LAI, 51.2% for oral; P = 0.60), or relapse rate (20.1% for LAI, 18.5% for oral; P = 0.66). Postbaseline psychiatric hospitalization rate was low for both groups (7.6% for LAI, 9.2% for oral), but mean hospitalization duration was significantly longer for oral patients (1.80 days [20 for those hospitalized] vs 0.43 days [6 for those hospitalized], P = 0.02). There were no clinically significant group differences in adverse events or safety measures. No post-injection delirium/sedation syndrome events occurred. In conclusion, olanzapine LAI and oral olanzapine were similarly effective and well tolerated for up to 2 years of treatment in patients with schizophrenia. Treatment discontinuation for olanzapine LAI was similar to that of oral olanzapine, despite the 3-hour post-injection observation period and other precautionary procedures related to risk of post-injection delirium/sedation syndrome. PMID:24781441

  9. Short-course eflornithine in Gambian trypanosomiasis: a multicentre randomized controlled trial.

    PubMed Central

    Pépin, J.; Khonde, N.; Maiso, F.; Doua, F.; Jaffar, S.; Ngampo, S.; Mpia, B.; Mbulamberi, D.; Kuzoe, F.

    2000-01-01

    OBJECTIVE: A randomized controlled trial was conducted to determine whether 7 days of intravenous eflornithine (100 mg/kg every 6 h) was as effective as the standard 14-day regimen in the treatment of late-stage Trypanosoma brucei gambiense trypanosomiasis. METHODS: A total of 321 patients (274 new cases, 47 relapsing cases) were randomized at four participating centres in Congo, Côte d'Ivoire, the Democratic Republic of the Congo, and Uganda to one of these treatment regimens and followed up for 2 years. RESULTS: Six patients died during treatment, one of whom was on the 7-day regimen, whereas the other five had been on the 14-day regimen (P = 0.2). The response to eflornithine differed markedly between Uganda and other countries. Among new cases in Uganda, the 2-year probability of cure was 73% on the 14-day course compared with 62% on the 7-day regimen (hazard ratio (HR) for treatment failure, 7-day versus 14-day regimen: 1.45, 95% CI: 0.7, 3.1, P = 0.3). Among new cases in Côte d'Ivoire, Congo, and the Democratic Republic of the Congo combined, the 2-year probability of cure was 97% on the 14-day course compared with 86.5% on the 7-day regimen (HR for treatment failure, 7-day vs 14-day: 6.72, 95% confidence interval (CI): 1.5, 31.0, P = 0.003). Among relapsing cases in all four countries, the 2-year probability of cure was 94% with 7 days and 100% with 14 days of treatment. Factors associated with a higher risk of treatment failure were: a positive lymph node aspirate (HR 4.1; 95% CI: 1.8-9.4), a cerebrospinal fluid (CSF) white cell count > or = 100/mm3 (HR 3.5; 95% CI: 1.1-10.9), being treated in Uganda (HR 2.9; 95% CI: 1.4-5.9), and CSF trypanosomes (HR 1.9; 95% CI: 0.9-4.1). Being stuporous on admission was associated with a lower risk of treatment failure (HR 0.18; 95% CI: 0.02-1.4) as was increasing age (HR 0.977; 95% CI: 0.95-1.0, for each additional year of age). DISCUSSION: The 7-day course of eflornithine is an effective treatment of relapsing cases

  10. Randomized comparison between the cemented Scientific Hip Prosthesis and Omnifit: 2-year DEXA and minimum 10-year clinical follow-up.

    PubMed

    Broeke, René H M Ten; Harings, Steffie E J M; Emans, Pieter J; Jutten, Liesbeth M C; Kessels, Alfons G H; Geesink, Rudolph G T

    2013-09-01

    Radiostereometry (RSA) of the cemented Scientific Hip Prosthesis (SHP) reported excessive migration and predicted high failure rates. In a prospective randomized clinical trial we compared minimum 10 years results of the SHP (n=38) with the Omnifit-stem (n=37). Two-year bone remodelling, compared with dual energy x-ray absorptiometry and assessed in regions of interest A-D based on the 7 Gruen zones, showed better periprosthetic bone preservation around the SHP in all but one regions (P<.05). At 10 years Harris Hip Score was better for the SHP (P=.0001) but Oxford Hip Score was the same (P=.79). There were no revisions in either group, but radiographic loosening was definite in 1 SHP and 1 Omnifit. Based on earlier RSA studies, the rough surface finish of the SHP was expected to cause cement abrasion, osteolysis and inferior survival. However our clinical and remodelling results could not confirm these expectations, suggesting that the link of early migration and mid-term clinical results is not sufficiently clear for the SHP. PMID:23453292

  11. Effects of resistance training on sarcopenic obesity index in older women: A randomized controlled trial.

    PubMed

    Gadelha, André Bonadias; Paiva, Flávio Macedo Lahud; Gauche, Rafael; de Oliveira, Ricardo Jacó; Lima, Ricardo Moreno

    2016-01-01

    The purpose of this study was to examine the effects of resistance training (RT) on sarcopenic obesity (SO) in older women. 243 older women underwent body composition measurement using dual-energy X-ray absorptiometry, and the SO index was calculated. This randomized controlled trial adopted from the baseline sample, 113 volunteers (67.0±5.2years) were randomly assigned to a control group (CG, n=64) or an experimental group (EG, n=69). The EG took part in a 24-week RT program, conducted three times per week. Body composition measurements were repeated at the end of the training program. RT induced a significant increase in fat-free mass (P<0.01), but not decrease in fat mass in the EG. Moreover, the SO index was also significantly improved in the EG (P<0.01), while it decreased significantly in the CG (P<0.01). It is concluded that RT is an effective approach to promote body composition alterations in older women, and it might improve SO-related phenotypes. PMID:27057600

  12. A Cluster Randomized Controlled Evaluation of the Health Impact of a Novel Antimicrobial Hand Towel on the Health of Children Under 2 Years Old in Rural Communities in Nyanza Province, Kenya.

    PubMed

    Slayton, Rachel B; Murphy, Jennifer L; Morris, Jamae; Faith, Sitnah Hamidah; Oremo, Jared; Odhiambo, Aloyce; Ayers, Tracy; Feinman, Shawna J; Brown, Allison C; Quick, Robert E

    2016-02-01

    To assess the health impact of reusable, antimicrobial hand towels, we conducted a cluster randomized, yearlong field trial. At baseline, we surveyed mothers, and gave four towels plus hygiene education to intervention households and education alone to controls. At biweekly home visits, we asked about infections in children < 2 years old and tested post-handwashing hand rinse samples of 20% of mothers for Escherichia coli. At study's conclusion, we tested 50% of towels for E. coli. Baseline characteristics between 188 intervention and 181 control households were similar. Intervention and control children had similar rates of diarrhea (1.47 versus 1.48, P = 0.99), respiratory infections (1.38 versus 1.48, P = 0.92), skin infections (1.76 versus 1.79, P = 0.81), and subjective fever (2.62 versus 3.40, P = 0.04) per 100 person-visits. Post-handwashing hand contamination was similar; 67% of towels exhibited E. coli contamination. Antimicrobial hand towels became contaminated over time, did not improve hand hygiene, or prevent diarrhea, respiratory infections, or skin infections. PMID:26643530

  13. Mexican American Trial of Community Health Workers: A Randomized Controlled Trial of a Community Health Worker Intervention for Mexican Americans With Type 2 Diabetes Mellitus

    PubMed Central

    Martin, Molly A.; Swider, Susan M.; Tumialán Lynas, Carmen M.; Janssen, Imke; Avery, Elizabeth F.; Powell, Lynda H.

    2014-01-01

    Objectives. We assessed whether community health workers (CHWs) could improve glycemic control among Mexican Americans with diabetes. Methods. We recruited 144 Mexican Americans with type 2 diabetes between January 2006 and September 2008 into the single-blinded, randomized controlled Mexican American Trial of Community Health Workers (MATCH) and followed them for 2 years. Participants were assigned to either a CHW intervention, delivering self-management training through 36 home visits over 2 years, or a bilingual control newsletter delivering the same information on the same schedule. Results. Intervention participants showed significantly lower hemoglobin A1c levels than control participants at both year 1 Δ = −0.55; P = .021) and year 2 (Δ = −0.69; P = .005). We observed no effect on blood pressure control, glucose self-monitoring, or adherence to medications or diet. Intervention participants increased physical activity from a mean of 1.63 days per week at baseline to 2.64 days per week after 2 years. Conclusions. A self-management intervention delivered by CHWs resulted in sustained improvements in glycemic control over 2 years among Mexican Americans with diabetes. MATCH adds to the growing body of evidence supporting the use of CHWs to reduce diabetes-related health disparities. PMID:23947316

  14. Randomized control trial of computer-based rehabilitation of spatial neglect syndrome: the RESPONSE trial protocol

    PubMed Central

    2014-01-01

    Background Spatial neglect is a frequent and debilitating consequence of acquired brain injury and currently has no widely accepted standard of care. While previous interventions for spatial neglect have targeted patients’ overt spatial deficits (e.g., reduced contralesional visual scanning), far fewer have directly targeted patients’ non-spatial deficits (e.g., sustained attention deficits). Considering that non-spatial deficits have shown to be highly predictive of long-term disability, we developed a novel computer based training program that targets both sustained (tonic) and moment-to-moment (phasic) aspects of non-spatial attention (Tonic and Phasic Alertness Training, TAPAT). Preliminary studies demonstrate that TAPAT is safe and effective in improving both spatial and non-spatial attention deficits in the post-acute recovery phase in neglect patients. The purpose of the current trial (referred to as the REmediation of SPatial Neglect or RESPONSE trial) is to compare TAPAT to an active control training condition, include a larger sample of patients, and assess both cognitive and functional outcomes. Methods/Design We will employ a multi-site, longitudinal, blinded randomized controlled trial (RCT) design with a target sample of 114 patients with spatial neglect. Patients will either perform, at their home, the experimental TAPAT training program or an active control computer games condition for thirty minutes/day, five days a week, over three months. Patients will be assessed on a battery of cognitive and functional outcomes on three occasions: a) immediately before training, b) within forty-eight hours post completion of total training, and c) after a three-month no-contact period post completion of total training, to assess the longevity of potential training effects. Discussion The strengths of this protocol are that it tests an innovative, in-home administered treatment that targets a fundamental deficit in neglect, employs highly sensitive computer

  15. A randomized controlled trial of group Stepping Stones Triple P: a mixed-disability trial.

    PubMed

    Roux, Gemma; Sofronoff, Kate; Sanders, Matthew

    2013-09-01

    Stepping Stones Triple P (SSTP) is a parenting program designed for families of a child with a disability. The current study involved a randomized controlled trial of Group Stepping Stones Triple P (GSSTP) for a mixed-disability group. Participants were 52 families of children diagnosed with an Autism Spectrum Disorder, Down syndrome, Cerebral Palsy, or an intellectual disability. The results demonstrated significant improvements in parent-reported child behavior, parenting styles, parental satisfaction, and conflict about parenting. Results among participants were similar despite children's differing impairments. The intervention effect was maintained at 6-month follow-up. The results indicate that GSSTP is a promising intervention for a mixed-disability group. Limitations of the study, along with areas for future research, are also discussed. PMID:24033239

  16. A Randomized, Controlled Trial of Magnesium Sulfate for the Prevention of Cerebral Palsy

    PubMed Central

    Rouse, Dwight J.; Hirtz, Deborah G.; Thom, Elizabeth; Varner, Michael W.; Spong, Catherine Y.; Mercer, Brian M.; Iams, Jay D.; Wapner, Ronald J.; Sorokin, Yoram; Alexander, James M.; Harper, Margaret; Thorp, John M.; Ramin, Susan M.; Malone, Fergal D.; Carpenter, Marshall; Miodovnik, Menachem; Moawad, Atef; O'Sullivan, Mary J.; Peaceman, Alan M.; Hankins, Gary D.V.; Langer, Oded; Caritis, Steve N.; Roberts, James M.

    2009-01-01

    BACKGROUND Research suggests that fetal exposure to magnesium sulfate before preterm birth might reduce the risk of cerebral palsy. METHODS In this multicenter, placebo-controlled, double-blind trial, we randomly assigned women at imminent risk for delivery between 24 and 31 weeks of gestation to receive magnesium sulfate, administered intravenously as a 6-g bolus followed by a constant infusion of 2 g per hour, or matching placebo. The primary outcome was the composite of stillbirth or infant death by 1 year of corrected age or moderate or severe cerebral palsy at or beyond 2 years of corrected age. RESULTS A total of 2241 women underwent randomization. The baseline characteristics were similar in the two groups. Follow-up was achieved for 95.6% of the children. The rate of the primary outcome was not significantly different in the magnesium sulfate group and the placebo group (11.3% and 11.7%, respectively; relative risk, 0.97; 95% confidence interval [CI], 0.77 to 1.23). However, in a prespecified secondary analysis, moderate or severe cerebral palsy occurred significantly less frequently in the magnesium sulfate group (1.9% vs. 3.5%; relative risk, 0.55; 95% CI, 0.32 to 0.95). The risk of death did not differ significantly between the groups (9.5% vs. 8.5%; relative risk, 1.12; 95% CI, 0.85 to 1.47). No woman had a life-threatening event. CONCLUSIONS Fetal exposure to magnesium sulfate before anticipated early preterm delivery did not reduce the combined risk of moderate or severe cerebral palsy or death, although the rate of cerebral palsy was reduced among survivors. (ClinicalTrials.gov number, NCT00014989.) PMID:18753646

  17. Randomized Trial of Transcranial Direct Current Stimulation and Hearing Aids for Tinnitus Management.

    PubMed

    Shekhawat, Giriraj Singh; Searchfield, Grant D; Stinear, Cathy M

    2013-11-01

    Background. The perception of sound in the absence of an external sound is tinnitus. Tinnitus can have a severe negative impact on quality of life. Objective. This trial investigated whether multisession anodal transcranial direct current stimulation (tDCS) of the left temporoparietal area would enhance sound therapy from hearing aids. Methods. Forty participants (mean age = 54 years) experiencing chronic tinnitus (minimum 2 years) completed a 7-month long double-blind randomized clinical trial. Participants were randomized into 2 groups: control receiving sham tDCS and experimental receiving tDCS. Each group underwent multisession (5 consecutive sessions with 24-hour gap) anodal tDCS (2 mA intensity and 20 minutes duration) of the left temporoparietal area, followed by hearing aid use for 6 months. The impact of tDCS and hearing aid use on tinnitus was assessed using questionnaires (primary measure: Tinnitus Functional Index) and minimum masking level measurement. Results. There was a significant reduction in the overall Tinnitus Functional Index score with time, F(2, 37) = 11.9, P = .0001, for both the groups. Similar patterns were seen for secondary measures. tDCS appeared to have a positive effect on minimum masking levels but not questionnaire responses. Conclusions. After 3 months of hearing aid use, there were significant improvements in tinnitus, which were sustained at 6 months of use. The hearing aid effects appeared independent of tDCS. Further investigations of tDCS or other neuromodulators priming the auditory system for sound therapy based tinnitus treatments are warranted. PMID:24213961

  18. Prevention trial in the Cherokee Nation: design of a randomized community trial.

    PubMed

    Komro, Kelli A; Wagenaar, Alexander C; Boyd, Misty; Boyd, B J; Kominsky, Terrence; Pettigrew, Dallas; Tobler, Amy L; Lynne-Landsman, Sarah D; Livingston, Melvin D; Livingston, Bethany; Molina, Mildred M Maldonado

    2015-02-01

    Despite advances in prevention science and practice in recent decades, the U.S. continues to struggle with significant alcohol-related risks and consequences among youth, especially among vulnerable rural and Native American youth. The Prevention Trial in the Cherokee Nation is a partnership between prevention scientists and Cherokee Nation Behavioral Health to create, implement, and evaluate a new, integrated community-level intervention designed to prevent underage drinking and associated negative consequences among Native American and other youth living in rural high-risk underserved communities. The intervention builds directly on results of multiple previous trials of two conceptually distinct approaches. The first is an updated version of CMCA, an established community environmental change intervention, and the second is CONNECT, our newly developed population-wide intervention based on screening, brief intervention, and referral to treatment (SBIRT) research. CMCA direct-action community organizing is used to engage local citizens to address community norms and practices related to alcohol use and commercial and social access to alcohol among adolescents. The new CONNECT intervention expands traditional SBIRT to be implemented universally within schools. Six key research design elements optimize causal inference and experimental evaluation of intervention effects, including a controlled interrupted time-series design, purposive selection of towns, random assignment to study condition, nested cohorts as well as repeated cross-sectional observations, a factorial design crossing two conceptually distinct interventions, and multiple comparison groups. The purpose of this paper is to describe the strong partnership between prevention scientists and behavioral health leaders within the Cherokee Nation, and the intervention and research design of this new community trial. PMID:24615546

  19. Amoxicillin for acute rhinosinusitis: A randomized controlled trial

    PubMed Central

    Garbutt, Jane M.; Banister, Christina; Spitznagel, Edward; Piccirillo, Jay F.

    2013-01-01

    Context Evidence to support antibiotic treatment for acute rhinosinusitis is scant, yet antibiotics are commonly used. Objective To determine the incremental effect of amoxicillin treatment over symptomatic treatments for adults with clinically diagnosed acute rhinosinusitis. Design Randomized placebo-controlled trial Participants and Setting Adults with uncomplicated, acute rhinosinusitis were recruited from 10 community practices in Missouri between November 1st 2006 and May 1st 2009 Interventions Ten-day course of either amoxicillin (1500mg/day) or placebo administered in three doses/day. All patients received a 5-7-day supply of symptomatic treatments for pain, fever, cough and nasal congestion to use as needed. Main Outcome Measures The primary outcome was improvement in the disease-specific quality of life after 3–4 days of treatment assessed with the SNOT-16 (minimally important difference 0.5 on 0 to 3 scale). Secondary outcomes included the patients' retrospective assessment of change in sinus symptoms and functional status, recurrence or relapse, satisfaction with and adverse effects of treatment. Outcomes were assessed by telephone interview at Days 3, 7, 10 and 28. Results 166 adults (36% male, 78% Caucasian) were randomized to amoxicillin (85) or placebo (81); 92% concurrently used ≥1 symptomatic treatment (amoxicillin, 94%, placebo 90%, p=0.34). The mean change in SNOT-16 scores was not significantly different between groups on Day 3 (mean difference between groups 0.03, 95% CI −0.12 to 0.19) and Day 10, but differed at Day 7 favoring amoxicillin (mean difference between groups 0.19, 95% CI 0.024 to 0.35). At Day 7 more participants treated with amoxicillin reported symptom improvement (74% vs. 56%, p=0.0205; NNT = 6, 95% CI 3 to 34), with no difference at Day-3 or Day-10. No between group differences were found for any other secondary outcomes. No serious adverse events occurred. Conclusion Among patients with acute rhinosinusitis, a 10-day

  20. Randomized controlled trial of atorvastatin in clinically isolated syndrome

    PubMed Central

    Waubant, E.; Pelletier, D.; Mass, M.; Cohen, J.A.; Kita, M.; Cross, A.; Bar-Or, A.; Vollmer, T.; Racke, M.; Stüve, O.; Schwid, S.; Goodman, A.; Kachuck, N.; Preiningerova, J.; Weinstock-Guttman, B.; Calabresi, P.A.; Miller, A.; Mokhtarani, M.; Iklé, D.; Murphy, S.; Kopetskie, H.; Ding, L.; Rosenberg, E.; Spencer, C.; Zamvil, S.S.; Waubant, E.; Pelletier, D.; Mass, M.; Bourdette, D.; Egan, R.; Cohen, J.; Stone, L.; Kita, M.; Elliott, M.; Cross, A.; Parks, B.J.; Bar-Or, A.; Vollmer, T.; Campagnolo, D.; Racke, M.; Stüve, O.; Frohman, E.; Schwid, S.; Goodman, A.; Segal, B.; Kachuck, N.; Weiner, L.; Preiningerova, J.; Carrithers, M.; Weinstock-Guttman, B.; Calabresi, P.; Kerr, D.; Miller, A.; Lublin, F.; Sayre, Peter; Hayes, Deborah; Rosenberg, Ellen; Gao, Wendy; Ding, Linna; Adah, Steven; Mokhtarani, Masoud; Neuenburg, Jutta; Bromstead, Carolyn; Olinger, Lynn; Mullen, Blair; Jamison, Ross; Speth, Kelly; Saljooqi, Kerensa; Phan, Peter; Phippard, Deborah; Seyfert-Margolis, Vicki; Bourcier, Katarzyna; Debnam, Tracia; Romaine, Jennifer; Wolin, Stephanie; O'Dale, Brittany; Iklé, David; Murphy, Stacey; Kopetskie, Heather

    2012-01-01

    Objective: To test efficacy and safety of atorvastatin in subjects with clinically isolated syndrome (CIS). Methods: Subjects with CIS were enrolled in a phase II, double-blind, placebo-controlled, 14-center randomized trial testing 80 mg atorvastatin on clinical and brain MRI activity. Brain MRIs were performed quarterly. The primary endpoint (PEP) was development of ≥3 new T2 lesions, or one clinical relapse within 12 months. Subjects meeting the PEP were offered additional weekly interferon β-1a (IFNβ-1a). Results: Due to slow recruitment, enrollment was discontinued after 81 of 152 planned subjects with CIS were randomized and initiated study drug. Median (interquartile range) numbers of T2 and gadolinium-enhancing (Gd) lesions were 15.0 (22.0) and 0.0 (0.0) at baseline. A total of 53.1% of atorvastatin recipients (n = 26/49) met PEP compared to 56.3% of placebo recipients (n = 18/32) (p = 0.82). Eleven atorvastatin subjects (22.4%) and 7 placebo subjects (21.9%) met the PEP by clinical criteria. Proportion of subjects who did not develop new T2 lesions up to month 12 or to starting IFNβ-1a was 55.3% in the atorvastatin and 27.6% in the placebo group (p = 0.03). Likelihood of remaining free of new T2 lesions was significantly greater in the atorvastatin group compared with placebo (odds ratio [OR] = 4.34, p = 0.01). Likelihood of remaining free of Gd lesions tended to be higher in the atorvastatin group (OR = 2.72, p = 0.11). Overall, atorvastatin was well tolerated. No clear antagonistic effect of atorvastatin plus IFNβ-1a was observed on MRI measures. Conclusion: Atorvastatin treatment significantly decreased development of new brain MRI T2 lesion activity, although it did not achieve the composite clinical and imaging PEP. Classification of Evidence: This study provided Class II evidence that atorvastatin did not reduce the proportion of patients with CIS meeting imaging and clinical criteria for starting immunomodulating therapy after 12 months

  1. Extracranial-Intracranial Bypass Surgery for Stroke Prevention in Hemodynamic Cerebral Ischemia: The Carotid Occlusion Surgery Study: A Randomized Trial

    PubMed Central

    Powers, William J.; Clarke, William R.; Grubb, Robert L.; Videen, Tom O; Adams, Harold P.; Derdeyn, Colin P.

    2013-01-01

    Context Patients with symptomatic atherosclerotic internal carotid artery occlusion (AICAO) and hemodynamic cerebral ischemia are at high risk for subsequent stroke when treated medically. Objective Test the hypothesis that extracranial-intracranial (EC-IC) bypass surgery, added to best medical therapy, reduces subsequent ipsilateral ischemic stroke in patients with recently symptomatic AICAO and hemodynamic cerebral ischemia. Design Parallel group, randomized, open-label, blinded-adjudication clinical treatment trial conducted from 2002–2010. Setting 49 clinical centers and 18 positron emission tomography (PET) centers in the United States and Canada. The majority were academic medical centers. Participants Arteriographically-confirmed AICAO causing hemispheric symptoms within 120 days and hemodynamic cerebral ischemia identified by ipsilateral increased oxygen extraction fraction measured by PET. 195 were randomized: 97 to surgery and 98 to no surgery. Follow-up for the primary endpoint until occurrence, 2 years, or end of trial was 99% complete. No participant withdrew because of adverse events. Interventions Anastomosis of superficial temporal artery branch to a middle cerebral artery cortical branch for the surgical group. Anti-thrombotic therapy and risk factor intervention were recommended for all. Main Outcome Measure For all participants who were assigned to surgery and received surgery, the combination of (1) all stroke and death from surgery through 30 days post surgery and (2) ipsilateral ischemic stroke within 2 years of randomization. For the nonsurgical group and participants assigned to surgery who did not receive surgery was the combination of (1) all stroke and death from randomization to randomization plus 30 days and (2) ipsilateral ischemic stroke within two years of randomization. Results The trial was terminated early for futility. Two-year rates for the primary endpoint were 21.0% (95% CI, 12.8% to 29.2%; 20 events) for the surgical group

  2. Using an informed consent in mammography screening: a randomized trial.

    PubMed

    Baena-Cañada, José M; Rosado-Varela, Petra; Expósito-Álvarez, Inmaculada; González-Guerrero, Macarena; Nieto-Vera, Juan; Benítez-Rodríguez, Encarnación

    2015-12-01

    Spanish women do not make an informed choice regarding breast cancer screening (BCS). Our aim was to evaluate the impact of receiving information regarding real BCS benefits and risks on knowledge, attitude, decision, feelings, and worries about cancer. Randomized controlled clinical trial of 355 women aged between 45 and 67 years, 177 and 178 assigned to the intervention group (IG) and control group (CG), respectively. After breast screening, women received either Nordic Cochrane Centre information on BCS or standard information. The primary outcome (knowledge) was determined from questionnaire administered at baseline and after a month. Answers were scored from 0 to 10 and scores of 5 or more indicated that women were well informed (had "good knowledge"). Questionnaires regarding attitudes, future screening intentions, and psychosocial impact were also administered. The Chi-squared and Student's t-tests were used to compare qualitative and quantitative variables, respectively. Good knowledge was acquired by 32 (18.10%) IG women and 15 (8.40%) CG women (P = 0.008). Mean scores from first to second interview increased from 2.97 (SD 1.16) to 3.43 (SD 1.39) in the CG and from and from 2.96 (SD 1.23) to 3.95 (SD 1.78) (P = 0.002) in the IG. No differences were found in the secondary endpoints. Women receiving information based on the Nordic Cochrane Centre document were better informed. This means of providing information is not very efficacious, nor does it modify attitude, decision, feelings, or worries about cancer. PMID:26377150

  3. Transdermal Estradiol Treatment for Postpartum Depression: A Pilot, Randomized Trial.

    PubMed

    Wisner, Katherine L; Sit, Dorothy K Y; Moses-Kolko, Eydie L; Driscoll, Kara E; Prairie, Beth A; Stika, Catherine S; Eng, Heather F; Dills, John L; Luther, James F; Wisniewski, Stephen R

    2015-08-01

    Postpartum depression occurs in 14.5% of women in the first 3 months after birth. This study was an 8-week acute phase randomized trial with 3 cells (transdermal estradiol [E2], sertraline [SERT], and placebo [PL]) for the treatment of postpartum major depressive disorder. However, the study was stopped after batch analysis revealed that the E2 serum concentrations were lower than prestudy projections. This paper explores our experiences that will inform future investigations of therapeutic E2 use. Explanations for the low E2 concentrations were as follows: (1) study patch nonadhesion, which did not explain the low concentrations across the entire sample. (2) Ineffective transdermal patch preparations, although 2 different patch preparations were used and no significant main effect of patch type on E2 concentrations was found. (3) Obesity, at study entry, E2-treated women had body mass index of 32.9 (7.4) (mean [SD]). No pharmacokinetic data comparing E2 concentrations from transdermal patches in obese women versus normal weight controls are available. (4) Induction of cytochrome P450 (CYP450) 3A4 and other E2 elimination pathways in pregnancy. CYP4503A4 is induced in pregnancy and is a pathway for the metabolism of E2. Conversion to estrone and phase II metabolism via glucuronidation and sulfation, which also increase in pregnancy, are routes of E2 elimination. The time required for these pathways to normalize after delivery has not been elucidated. The observation that transdermal E2 doses greater than 100 μg/d did not increase serum concentrations was unexpected. Another hypothesis consistent with this observation is suppression of endogenous E2 secretion with increasing exogenous E2 dosing. PMID:26061609

  4. Dietary Fiber Supplementation for Fecal Incontinence: A Randomized Clinical Trial

    PubMed Central

    Bliss, Donna Z.; Savik, Kay; Jung, Hans-Joachim G.; Whitebird, Robin; Lowry, Ann; Sheng, Xioayan

    2014-01-01

    Dietary fiber supplements are used to manage fecal incontinence (FI), but little is known about the fiber type to recommend or the level of effectiveness of such supplements, which appear related to the fermentability of the fiber. The aim of this single-blind, randomized controlled trial was to compare the effects of three dietary fiber supplements (carboxymethylcellulose [CMC], gum arabic [GA], or psyllium) with differing levels of fermentability to a placebo in community-living individuals incontinent of loose/liquid feces. The primary outcome was FI frequency; secondary outcomes included FI amount and consistency, supplement intolerance, and quality of life (QoL). Possible mechanisms underlying supplement effects were also examined. After a 14-day baseline, 189 subjects consumed a placebo or 16g total fiber/day of one of the fiber supplements for 32 days. FI frequency significantly decreased after psyllium supplementation versus placebo, in both intent-to-treat and per-protocol mixed model analyses. CMC increased FI frequency. In intent-to-treat analysis, the number of FI episodes/week after supplementation was estimated to be 5.5 for Placebo, 2.5 for Psyllium, 4.3 for GA, and 6.2 for CMC. Only psyllium consumption resulted in a gel in feces. Supplement intolerance was low. QoL scores did not differ among groups. Patients with FI may experience a reduction in FI frequency after psyllium supplementation, and decreased FI frequency has been shown to be an important personal goal of treatment for patients with FI. Formation of a gel in feces appears to be a mechanism by which residual psyllium improved FI. PMID:25155992

  5. Nutrition intervention for migraine: a randomized crossover trial

    PubMed Central

    2014-01-01

    Background Limited evidence suggests that dietary interventions may offer a promising approach for migraine. The purpose of this study was to determine the effects of a low-fat plant-based diet intervention on migraine severity and frequency. Methods Forty-two adult migraine sufferers were recruited from the general community in Washington, DC, and divided randomly into two groups. This 36-week crossover study included two treatments: dietary instruction and placebo supplement. Each treatment period was 16 weeks, with a 4-week washout between. During the diet period, a low-fat vegan diet was prescribed for 4 weeks, after which an elimination diet was used. Participants were assessed at the beginning, midpoint, and end of each period. Significance was determined using student’s t-tests. Results Worst headache pain in last 2 weeks, as measured by visual analog scale, was initially 6.4/10 cm (SD 2.1 cm), and declined 2.1 cm during the diet period and 0.7 cm during the supplement period (p=0.03). Average headache intensity (0–10 scale) was initially 4.2 (SD 1.4) per week, and this declined by 1.0 during the diet period and by 0.5 during the supplement period (p=0.20). Average headache frequency was initially 2.3 (SD 1.8) per week, and this declined by 0.3 during the diet period and by 0.4 during the supplement period (p=0.61). The Patient’s Global Impression of Change showed greater improvement in pain during the diet period (p<0.001). Conclusions These results suggest that a nutritional approach may be a useful part of migraine treatment, but that methodologic issues necessitate further research. Trial registration Clinicaltrials.gov, NCT01699009 and NCT01547494. PMID:25339342

  6. Workplace based mindfulness practice and inflammation: a randomized trial.

    PubMed

    Malarkey, William B; Jarjoura, David; Klatt, Maryanna

    2013-01-01

    We have developed a low dose Mindfulness-Based Intervention (MBI-ld) that reduces the time committed to meetings and formal mindfulness practice, while conducting the sessions during the workday. This reduced the barriers commonly mentioned for non-participation in mindfulness programs. In a controlled randomized trial we studied university faculty and staff (n=186) who were found to have an elevated CRP level,>3.0 mg/ml, and who either had, or were at risk for cardiovascular disease. This study was designed to evaluate if MBI-ld could produce a greater decrease in CRP, IL-6 and cortisol than an active control group receiving a lifestyle education program when measured at the end of the 2 month interventions. We found that MBI-ld significantly enhanced mindfulness by 2-months and it was maintained for up to a year when compared to the education control. No significant changes were noted between interventions in cortisol, IL-6 levels or self-reported measures of perceived stress, depression and sleep quality at 2-months. Although not statistically significant (p=.08), the CRP level at 2-months was one mg/ml lower in the MBI-ld group than in the education control group, a change which may have clinical significance (Ridker et al., 2000; Wassel et al., 2010). A larger MBI-ld effect on CRP (as compared to control) occurred among participants who had a baseline BMI <30 (-2.67 mg/ml) than for those with BMI >30 (-0.18 mg/ml). We conclude that MBI-ld should be more fully investigated as a low-cost self-directed complementary strategy for decreasing inflammation, and it seems most promising for non-obese subjects. PMID:23078984

  7. Tryptophan Supplementation and Postoperative Delirium – A Randomized Controlled Trial

    PubMed Central

    Robinson, Thomas N.; Dunn, Christina L.; Adams, Jill C.; Hawkins, Carrie L.; Tran, Zung V.; Raeburn, Christopher D.; Moss, Marc

    2014-01-01

    Background/Objectives Tryptophan deficiency has been associated with increased incidence of postoperative delirium. Therefore, we hypothesized that the post-operative administration of tryptophan would be beneficial for elderly surgical patients who are at higher risk of developing post-operative delirium. Design Randomized, double-blind, placebo controlled trial. Setting: Participants A total of 325 individuals aged 60 years and older undergoing major elective operations requiring a postoperative intensive care unit admission. Intervention L-tryptophan, 1 gram orally, three times daily or placebo was started following the operation and continued for up to three days postoperatively. Measurements Delirium and its motor subtypes were measured using the Confusion Assessment Method-ICU and the Richmond Agitation and Sedation Scale. The primary outcome for between groups comparison was the incidence of excitatory (mixed and hyperactive) postoperative delirium. The secondary outcomes for comparison were the incidence and duration of overall postoperative delirium. Results The overall incidence of postoperative delirium was 39% (116) (95% confidence interval 34% to 44%). The percentages of patients with excitatory delirium in the tryptophan and placebo groups were 17% and 9% (p=0.176), and the duration of excitatory delirium was 3.3±1.7 and 3.1±1.9 days (p=0.741). The percentage of patients with overall delirium in the tryptophan and placebo groups was 40% and 37% (p=0.597), and the duration of overall delirium was 2.9±1.8 and 2.4±1.6 days (p=0.167). Conclusion Postoperative tryptophan supplementation in older adults undergoing major elective operations requiring postoperative intensive care unit admission demonstrated no efficacy in reducing the incidence of postoperative excitatory delirium or overall delirium, and the duration of excitatory or overall delirium. PMID:25112175

  8. Transdermal Estradiol Treatment for Postpartum Depression: A Pilot Randomized Trial

    PubMed Central

    Wisner, Katherine L.; Sit, Dorothy K.Y.; Moses-Kolko, Eydie L.; Driscoll, Kara E.; Prairie, Beth; Stika, Catherine S.; Eng, Heather F.; Dills, John L; Luther, James F.; Wisniewski, Stephen R.

    2015-01-01

    Postpartum depression occurs in 14.5% of women in the first three months after birth. This study was an 8 week acute phase randomized trial with three cells (transdermal estradiol (E2), sertraline, and placebo) for the treatment of postpartum major depressive disorder. However, the study was stopped after batch analysis revealed that the E2 serum concentrations were lower than pre-study projections. This paper explores our experiences that will inform future investigations of therapeutic E2 use. Explanations for the low E2 concentrations were: 1) Study patch non-adhesion, which did not explain the low concentrations across the entire sample. 2) Ineffective transdermal patch preparations, although two different patch preparations were used and no significant main effect of patch type on E2 concentrations was found. 3) Obesity, at study entry, E2-treated women had mean ± SD BMI=32.9 ±7.4. No pharmacokinetic data comparing E2 concentrations from transdermal patches in obese women vs. normal weight controls are available. 4) Induction of Cytochrome P450 (CYP450) 3A4 and other E2 elimination pathways in pregnancy. CYP4503A4 is induced in pregnancy and is a pathway for the metabolism of E2. Conversion to estrone and Phase II metabolism via glucuronidation and sulfation, which also increase in pregnancy, are routes of E2 elimination. The time required for these pathways to normalize after delivery has not been elucidated. The observation that transdermal E2 doses greater than 100 mcg/day did not increase serum concentrations was unexpected. Another hypothesis consistent with this observation is suppression of endogenous E2 secretion with increasing exogenous E2 dosing. PMID:26061609

  9. Modifying Media Content for Preschool Children: A Randomized Controlled Trial

    PubMed Central

    Garrison, Michelle M.; Herrenkohl, Todd; Haggerty, Kevin; Rivara, Frederick P.; Zhou, Chuan; Liekweg, Kimberly

    2013-01-01

    BACKGROUND: Although previous studies have revealed that preschool-aged children imitate both aggression and prosocial behaviors on screen, there have been few population-based studies designed to reduce aggression in preschool-aged children by modifying what they watch. METHODS: We devised a media diet intervention wherein parents were assisted in substituting high quality prosocial and educational programming for aggression-laden programming without trying to reduce total screen time. We conducted a randomized controlled trial of 565 parents of preschool-aged children ages 3 to 5 years recruited from community pediatric practices. Outcomes were derived from the Social Competence and Behavior Evaluation at 6 and 12 months. RESULTS: At 6 months, the overall mean Social Competence and Behavior Evaluation score was 2.11 points better (95% confidence interval [CI]: 0.78–3.44) in the intervention group as compared with the controls, and similar effects were observed for the externalizing subscale (0.68 [95% CI: 0.06–1.30]) and the social competence subscale (1.04 [95% CI: 0.34–1.74]). The effect for the internalizing subscale was in a positive direction but was not statistically significant (0.42 [95% CI: −0.14 to 0.99]). Although the effect sizes did not noticeably decay at 12 months, the effect on the externalizing subscale was no longer statistically significant (P = .05). In a stratified analysis of the effect on the overall scores, low-income boys appeared to derive the greatest benefit (6.48 [95% CI: 1.60–11.37]). CONCLUSIONS: An intervention to reduce exposure to screen violence and increase exposure to prosocial programming can positively impact child behavior. PMID:23420911

  10. The Steps to Health Randomized Trial for Arthritis

    PubMed Central

    Wilcox, Sara; McClenaghan, Bruce; Sharpe, Patricia A.; Baruth, Meghan; Hootman, Jennifer M.; Leith, Katherine; Dowda, Marsha

    2015-01-01

    Background Despite the established benefits of exercise for adults with arthritis, participation is low. Safe, evidence-based, self-directed programs, which have the potential for high reach at a low cost, are needed. Purpose To test a 12-week, self-directed, multicomponent exercise program for adults with arthritis. Design Randomized controlled trial. Data were collected from 2010 to 2012. Data were analyzed in 2013 and 2014. Setting/participants Adults with arthritis (N=401, aged 56.3 [10.7] years, 85.8% women, 63.8% white, 35.2% African American, BMI of 33.0 [8.2]) completed measures at a university research center and participated in a self-directed exercise intervention (First Step to Active Health®) or nutrition control program (Steps to Healthy Eating). Intervention Intervention participants received a self-directed multicomponent exercise program and returned self-monitoring logs for 12 weeks. Main outcome measures Self-reported physical activity, functional performance measures, and disease-specific outcomes (arthritis symptoms and self-efficacy) assessed at baseline, 12 weeks, and 9 months. Results Participants in the exercise condition showed greater increases in physical activity than those in the nutrition control group (p=0.01). Significant improvements, irrespective of condition, were seen in lower body strength, functional exercise capacity, lower body flexibility, pain, fatigue, stiffness, and arthritis management self-efficacy (p values <0.0001). More adverse events occurred in the exercise than nutrition control condition, but only one was severe and most were expected with increased physical activity. Conclusions The exercise program improves physical activity, and both programs improve functional and psychosocial outcomes. Potential reasons for improvements in the nutrition control condition are discussed. These interventions have the potential for large-scale dissemination. This study is registered at Clinicaltrials.gov NCT01172327. PMID

  11. A Randomized Trial of Rosuvastatin in the Prevention of Venous Thromboembolism: the JUPITER Trial

    PubMed Central

    Glynn, Robert J.; Danielson, Eleanor; Fonseca, Francisco AH; Genest, Jacques; Gotto, Antonio M.; Kastelein, John JP; Koenig, Wolfgang; Libby, Peter; Lorenzatti, Alberto J.; MacFadyen, Jean G.; Nordestgaard, Børge G.; Shepherd, James; Willerson, James T.; Ridker, Paul M

    2009-01-01

    Background Controversies persist on whether arterial and venous thrombosis share common pathways and whether treatments of known efficacy for one disease process have consistent benefits for the other. Observational studies have yielded variable estimates of the effect of statin therapy on risk of venous thromboembolism, and randomized evidence is lacking. Methods Symptomatic venous thromboembolism was a pre-specified endpoint of Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER). We randomly assigned 17,802 apparently healthy men and women with low-density lipoprotein (LDL) cholesterol levels of less than 130 mg/dL and high-sensitivity C-reactive protein levels of 2.0 mg/L or higher to rosuvastatin, 20 mg/d, or placebo. Intention-to-treat analyses followed participants for the first occurrence of pulmonary embolism or deep vein thrombosis. Results During a median follow-up of 1.9 years (maximum 5.0), symptomatic venous thromboembolism occurred in 94 participants, 34 in the rosuvastatin group and 60 in the placebo group. The rates of venous thromboembolism were 0.18 and 0.32 per 100 person-years of follow-up in the rosuvastatin and placebo groups, respectively (hazard ratio for rosuvastatin 0.57; 95% confidence interval [CI], 0.37 to 0.86; P=0.007), with corresponding rates of 0.10 and 0.17 for unprovoked venous thromboembolism (hazard ratio 0.61; 95% CI, 0.35 to 1.09; P=0.089) and 0.08 and 0.16 for provoked venous thromboembolism (hazard ratio 0.52; 95% CI, 0.28 to 0.96; P=0.033). Corresponding rates of pulmonary embolism were 0.09 and 0.12 (hazard ratio 0.77; 95% CI, 0.41 to 1.45; P=0.42), whereas rates of deep vein thrombosis only were 0.09 and 0.20 (hazard ratio 0.45; 95% CI, 0.25 to 0.79; P=0.004). Consistent effects were observed in all subgroups examined. No differences were seen between treatment groups in rates of bleeding. Conclusions In this trial of apparently healthy persons, rosuvastatin

  12. Central coordination as an alternative for local coordination in a multicenter randomized controlled trial: the FAITH trial experience

    PubMed Central

    2012-01-01

    Background Surgeons in the Netherlands, Canada and the US participate in the FAITH trial (Fixation using Alternative Implants for the Treatment of Hip fractures). Dutch sites are managed and visited by a financed central trial coordinator, whereas most Canadian and US sites have local study coordinators and receive per patient payment. This study was aimed to assess how these different trial management strategies affected trial performance. Methods Details related to obtaining ethics approval, time to trial start-up, inclusion, and percentage completed follow-ups were collected for each trial site and compared. Pre-trial screening data were compared with actual inclusion rates. Results Median trial start-up ranged from 41 days (P25-P75 10-139) in the Netherlands to 232 days (P25-P75 98-423) in Canada (p = 0.027). The inclusion rate was highest in the Netherlands; median 1.03 patients (P25-P75 0.43-2.21) per site per month, representing 34.4% of the total eligible population. It was lowest in Canada; 0.14 inclusions (P25-P75 0.00-0.28), representing 3.9% of eligible patients (p < 0.001). The percentage completed follow-ups was 83% for Canadian and Dutch sites and 70% for US sites (p = 0.217). Conclusions In this trial, a central financed trial coordinator to manage all trial related tasks in participating sites resulted in better trial progression and a similar follow-up. It is therefore a suitable alternative for appointing these tasks to local research assistants. The central coordinator approach can enable smaller regional hospitals to participate in multicenter randomized controlled trials. Circumstances such as available budget, sample size, and geographical area should however be taken into account when choosing a management strategy. Trial Registration ClinicalTrials.gov: NCT00761813 PMID:22225733

  13. Using second-order generalized estimating equations to model heterogeneous intraclass correlation in cluster randomized trials

    PubMed Central

    Crespi, Catherine M.; Wong, Weng Kee; Mishra, Shiraz I.

    2009-01-01

    SUMMARY In cluster randomized trials, it is commonly assumed that the magnitude of the correlation among subjects within a cluster is constant across clusters. However, the correlation may in fact be heterogeneous and depend on cluster characteristics. Accurate modeling of the correlation has the potential to improve inference. We use second-order generalized estimating equations to model heterogeneous correlation in cluster randomized trials. Using simulation studies we show that accurate modeling of heterogeneous correlation can improve inference when the correlation is high or varies by cluster size. We apply the methods to a cluster randomized trial of an intervention to promote breast cancer screening. PMID:19109804

  14. The Influence of Number of A Trials on 2-Year-Olds' Behavior in Two A-Not-B-Type Search Tasks: A Test of the Hierarchical Competing Systems Model

    ERIC Educational Resources Information Center

    Marcovitch, Stuart; Zelazo, Philip David

    2006-01-01

    Age-appropriate modifications of the A-not-B task were used to examine 2-year-olds' search behavior. Several theories predict that A-not-B errors will increase as a function of number of A trials. However, the hierarchical competing systems model (Marcovitch & Zelazo, 1999) predicts that although the ratio of perseverative to nonperseverative…

  15. Depression Prevention Research: Design, Implementation, and Analysis of Randomized Trials.

    ERIC Educational Resources Information Center

    Munoz, Ricardo F.; And Others

    This document contains three papers concerned with prevention intervention research, a new area of depression research which has shown great promise for contributing new knowledge to the understanding of depression. The first paper, "Clinical Trials vs. Prevention Trials: Methodological Issues in Depression Research" (Ricardo F. Munoz), emphasizes…

  16. OARSI Clinical Trials Recommendations: Key analytic considerations in design, analysis, and reporting of randomized controlled trials in osteoarthritis.

    PubMed

    Losina, E; Ranstam, J; Collins, J E; Schnitzer, T J; Katz, J N

    2015-05-01

    To highlight methodologic challenges pertinent to design, analysis, and reporting of results of randomized clinical trials in OA and offer practical suggestions to overcome these challenges. The topics covered in this paper include subject selection, randomization, approaches to handling missing data, subgroup analysis, sample size, and issues related to changing design mid-way through the study. Special attention is given to standardizing the reporting of results and economic analyses. Key findings include the importance of blinding and concealment, the distinction between superiority and non-inferiority trials, the need to minimize missing data, and appropriate analysis and interpretation of subgroup effects. Investigators may use the findings and recommendations advanced in this paper to guide design and conduct of randomized controlled trials of interventions for osteoarthritis. PMID:25952341

  17. Vitamin K Supplementation in Postmenopausal Women with Osteopenia (ECKO Trial): A Randomized Controlled Trial

    PubMed Central

    Cheung, Angela M; Tile, Lianne; Lee, Yuna; Tomlinson, George; Hawker, Gillian; Scher, Judy; Hu, Hanxian; Vieth, Reinhold; Thompson, Lilian; Jamal, Sophie; Josse, Robert

    2008-01-01

    Background Vitamin K has been widely promoted as a supplement for decreasing bone loss in postmenopausal women, but the long-term benefits and potential harms are unknown. This study was conducted to determine whether daily high-dose vitamin K1 supplementation safely reduces bone loss, bone turnover, and fractures. Methods and Findings This single-center study was designed as a 2-y randomized, placebo-controlled, double-blind trial, extended for earlier participants for up to an additional 2 y because of interest in long-term safety and fractures. A total of 440 postmenopausal women with osteopenia were randomized to either 5 mg of vitamin K1 or placebo daily. Primary outcomes were changes in BMD at the lumbar spine and total hip at 2 y. Secondary outcomes included changes in BMD at other sites and other time points, bone turnover markers, height, fractures, adverse effects, and health-related quality of life. This study has a power of 90% to detect 3% differences in BMD between the two groups. The women in this study were vitamin D replete, with a mean serum 25-hydroxyvitamin D level of 77 nmol/l at baseline. Over 2 y, BMD decreased by −1.28% and −1.22% (p = 0.84) (difference of −0.06%; 95% confidence interval [CI] −0.67% to 0.54%) at the lumbar spine and −0.69% and −0.88% (p = 0.51) (difference of 0.19%; 95% CI −0.37% to 0.75%) at the total hip in the vitamin K and placebo groups, respectively. There were no significant differences in changes in BMD at any site between the two groups over the 2- to 4-y period. Daily vitamin K1 supplementation increased serum vitamin K1 levels by 10-fold, and decreased the percentage of undercarboxylated osteocalcin and total osteocalcin levels (bone formation marker). However, C-telopeptide levels (bone resorption marker) were not significantly different between the two groups. Fewer women in the vitamin K group had clinical fractures (nine versus 20, p = 0.04) and fewer had cancers (three versus 12, p = 0

  18. A Data Management System Integrating Web-based Training and Randomized Trials: Requirements, Experiences and Recommendations

    PubMed Central

    Muroff, Jordana; Amodeo, Maryann; Larson, Mary Jo; Carey, Margaret; Loftin, Ralph D.

    2014-01-01

    This article describes a data management system (DMS) developed to support a large-scale randomized study of an innovative web-course that was designed to improve substance abuse counselors’ knowledge and skills in applying a substance abuse treatment method (i.e., cognitive behavioral therapy; CBT). The randomized trial compared the performance of web-course-trained participants (intervention group) and printed-manual-trained participants (comparison group) to determine the effectiveness of the web-course in teaching CBT skills. A single DMS was needed to support all aspects of the study: web-course delivery and management, as well as randomized trial management. The authors briefly reviewed several other systems that were described as built either to handle randomized trials or to deliver and evaluate web-based training. However it was clear that these systems fell short of meeting our needs for simultaneous, coordinated management of the web-course and the randomized trial. New England Research Institute’s (NERI) proprietary Advanced Data Entry and Protocol Tracking (ADEPT) system was coupled with the web-programmed course and customized for our purposes. This article highlights the requirements for a DMS that operates at the intersection of web-based course management systems and randomized clinical trial systems, and the extent to which the coupled, customized ADEPT satisfied those requirements. Recommendations are included for institutions and individuals considering conducting randomized trials and web-based training programs, and seeking a DMS that can meet similar requirements. PMID:25414571

  19. Efficacy and effectiveness as aspects of cluster randomized trials with nursing home residents: Methodological insights from a pneumonia prevention trial

    PubMed Central

    Van Ness, Peter H.; Peduzzi, Peter N.; Quagliarello, Vincent J.

    2012-01-01

    This report discusses how methodological aspects of study efficacy and effectiveness combine in cluster randomized trials in nursing homes. Discussion focuses on the relationships between these study aspects in the Pneumonia Reduction in Institutionalized Disabled Elders (PRIDE) trial, an ongoing cluster randomized clinical trial of pneumonia prevention among nursing home residents launched in October 2009 in Greater New Haven, Connecticut. This clinical trial has enrolled long-term care nursing home residents, over 65 years in age, who have either inadequate oral care or swallowing difficulty, previously identified risk factors for pneumonia. It has used a multicomponent intervention consisting of manual tooth/gum brushing, 0.12% chlorhexidine oral rinse administered twice daily by nurses, and upright feeding positioning at meals to reduce rates of radiographically documented pneumonia. Cluster randomization is attractive for nursing home intervention studies because physical proximity and administrative arrangements make it difficult to deliver different interventions to residents of the same nursing home. Implementing an intervention in an entire home requires integration into the daily life of residents and into the administrative procedures of the nursing home. This characteristic of nursing home cluster randomized trials makes them approximate “real-world” research contexts, but implementation can be challenging. The PRIDE trial of pneumonia prevention utilized specific methodological choices that include both efficacy and effectiveness elements. Cluster randomized trials in nursing homes having elements of both efficacy and effectiveness (i.e., hybrid designs) can address some of the methodological challenges of conducting clinical research in nursing homes; they have distinctive advantages and some limitations. PMID:22917599

  20. Gabapentin Treatment for Alcohol Dependence: A Randomized Controlled Trial

    PubMed Central

    Mason, Barbara J.; Quello, Susan; Goodell, Vivian; Shadan, Farhad; Kyle, Mark; Begovic, Adnan

    2013-01-01

    Importance Approved medications for alcohol dependence are prescribed for fewer than 9% of US alcoholics. Objective To determine if gabapentin, a widely-prescribed generic calcium channel/GABA modulating medication, increases rates of sustained abstinence and no heavy drinking, and decreases alcohol-related insomnia, dysphoria and craving, in a dose-dependent manner. Design, Participants and Setting A 12-week, double-blind, placebo-controlled, randomized dose-ranging trial of 150 men and women over 18 years of age with current alcohol dependence, conducted 2004–2010 at a single-site outpatient clinical research facility adjoining a general medical hospital. Interventions Oral gabapentin (0, 900, 1800 mg/d) and concomitant manual-guided counseling. Main Outcome Measures Rates of complete abstinence and no heavy drinking (co-primary) and changes in mood, sleep and craving (secondary) over the 12-week study. Results Gabapentin significantly improved the rates of abstinence and no heavy drinking. The abstinence rate was 4.1% (95% CI, 1.1 to 13.7) in the placebo group, 11.1% (95% CI, 5.2 to 22.2) in the 900 mg group, and 17.0% (95% CI, 8.9 to 30.1) in the 1800 mg group (p = 0.04 for linear dose effect, NNT = 8 for 1800 mg). The no heavy drinking rate was 22.5% (95% CI, 13.6 to 37.2) in the placebo group, 29.6% (95% CI, 19.1 to 42.8) in the 900 mg group, and 44.7% (95% CI, 31.4 to 58.8) in the 1800 mg group (p = 0.02 for linear dose effect, NNT = 5 for 1800 mg). Similar linear dose effects were obtained with measures of mood (F=7.37, df=2, p=0.001), sleep (F=136, df=2, p<0.001), and craving (F=3.56, df=2, p=0.029). There were no serious drug-related adverse events, and terminations from adverse-events (9 of 150 participants), time on study (9.1 [3.8] weeks) and rate of study completion (85 of 150 participants) did not differ between groups. Conclusions and Relevance Gabapentin (particularly the 1800 mg dosage) was effective in treating alcohol dependence and relapse

  1. Massage Therapy and Labor Outcomes: a Randomized Controlled Trial

    PubMed Central

    Janssen, Patricia; Shroff, Farah; Jaspar, Paula

    2012-01-01

    Introduction Massage is a time-honored method by which women have received comfort throughout the millennia, yet it has not been rigorously evaluated in the modern day delivery suite. No study to date that we are aware of has evaluated the effect of massage therapy by a regulated massage therapist on labor pain. The purpose of this study was to evaluate the effectiveness of massage therapy provided by registered massage therapists in managing pain among women in active labor. Methods BC Women’s Hospital, Vancouver, BC. Research Design: a randomized controlled trial. Participants: 77 healthy nulliparous women presenting in spontaneous labor. Intervention: Swedish massage administered for up to five hours by a registered massage therapist during labor vs. standard care. Main outcome measures include: cervical dilation at the time of administration of epidural, compared using estimated marginal means in an analysis of covariance. We also compared perception of pain at three time periods during labor according to cervical dilation at 3–4 cm, 5–7 cm, and 8–10 cm using the McGill Present Pain Intensity Scale. Results The mean cervical dilation at the time of epidural insertion after adjustment for station of the presenting part, cervical dilation, and status of membranes on admission to hospital was 5.9 cm (95% CI 5.2–6.7) compared to 4.9 in the control group (95% CI 4.2–5.8). Scores on the McGill Pain Scale were consistently lower in the massage therapy group (13.3 vs. 16.9 at 3–4 cm, 13.3 vs. 15.8 at 5–6 cm, and 19.4 vs. 28.3 at 7–8 cm), although these differences were not statistically significant. Conclusions Our findings from this pilot study suggest that massage therapy by a registered massage therapist has the potential to be an effective means of pain management that may be associated with delayed use of epidural analgesia. It may therefore have the potential to reduce exposure to epidural analgesia during labor and decrease rates of associated

  2. Intrathecal baclofen treatment in dystonic cerebral palsy: a randomized clinical trial: the IDYS trial

    PubMed Central

    2013-01-01

    Background Dystonic cerebral palsy is primarily caused by damage to the basal ganglia and central cortex. The daily care of these patients can be difficult due to dystonic movements. Intrathecal baclofen treatment is a potential treatment option for dystonia and has become common practice. Despite this widespread adoption, high quality evidence on the effects of intrathecal baclofen treatment on daily activities is lacking and prospective data are needed to judge the usefulness and indications for dystonic cerebral palsy. The primary aim of this study is to provide level one clinical evidence for the effects of intrathecal baclofen treatment on the level of activities and participation in dystonic cerebral palsy patients. Furthermore, we hope to identify clinical characteristics that will predict a beneficial effect of intrathecal baclofen in an individual patient. Methods/Design A double blind placebo-controlled multi-center randomized clinical trial will be performed in 30 children with dystonic cerebral palsy. Patients aged between 4 and 25 years old with a confirmed diagnosis of dystonic cerebral palsy, Gross Motor Functioning Classification System level IV or V, with lesions in the cerebral white matter, basal ganglia or central cortex and who are eligible for intrathecal baclofen treatment will be included. Group A will receive three months of continuous intrathecal baclofen treatment and group B will receive three months of placebo treatment, both via an implanted pump. After this three month period, all patients will receive intrathecal baclofen treatment, with a follow-up after nine months. The primary outcome measurement will be the effect on activities of and participation in daily life measured by Goal Attainment Scaling. Secondary outcome measurements on the level of body functions include dystonia, spasticity, pain, comfort and sleep-related breathing disorders. Side effects will be monitored and we will study whether patient characteristics

  3. Transparency of Outcome Reporting and Trial Registration of Randomized Controlled Trials Published in the Journal of Consulting and Clinical Psychology

    PubMed Central

    Azar, Marleine; Riehm, Kira E.; McKay, Dean; Thombs, Brett D.

    2015-01-01

    Background Confidence that randomized controlled trial (RCT) results accurately reflect intervention effectiveness depends on proper trial conduct and the accuracy and completeness of published trial reports. The Journal of Consulting and Clinical Psychology (JCCP) is the primary trials journal amongst American Psychological Association (APA) journals. The objectives of this study were to review RCTs recently published in JCCP to evaluate (1) adequacy of primary outcome analysis definitions; (2) registration status; and, (3) among registered trials, adequacy of outcome registrations. Additionally, we compared results from JCCP to findings from a recent study of top psychosomatic and behavioral medicine journals. Methods Eligible RCTs were published in JCCP in 2013–2014. For each RCT, two investigators independently extracted data on (1) adequacy of outcome analysis definitions in the published report, (2) whether the RCT was registered prior to enrolling patients, and (3) adequacy of outcome registration. Results Of 70 RCTs reviewed, 12 (17.1%) adequately defined primary or secondary outcome analyses, whereas 58 (82.3%) had multiple primary outcome analyses without statistical adjustment or undefined outcome analyses. There were 39 (55.7%) registered trials. Only two trials registered prior to patient enrollment with a single primary outcome variable and time point of assessment. However, in one of the two trials, registered and published outcomes were discrepant. No studies were adequately registered as per Standard Protocol Items: Recommendation for Interventional Trials guidelines. Compared to psychosomatic and behavioral medicine journals, the proportion of published trials with adequate outcome analysis declarations was significantly lower in JCCP (17.1% versus 32.9%; p = 0.029). The proportion of registered trials in JCCP (55.7%) was comparable to behavioral medicine journals (52.6%; p = 0.709). Conclusions The quality of published outcome analysis

  4. A randomized trial on folic acid supplementation and risk of recurrent colorectal adenoma

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Evidence from observational studies suggests that inadequate folate status enhances colorectal carcinogenesis, but results from some randomized trials do not support this hypothesis. Objective: To assess the effect of folic acid supplementation on recurrent colorectal adenoma, we conduc...

  5. Work, Recovery, and Comorbidity in Schizophrenia: A Randomized Controlled Trial of Cognitive Remediation

    PubMed Central

    McGurk, Susan R.; Mueser, Kim T.; DeRosa, Thomas J.; Wolfe, Rosemarie

    2009-01-01

    Employment is central to the concept of recovery in severe mental illness. However, common comorbid conditions present significant obstacles to consumers seeking employment and benefiting from vocational rehabilitation. We review research on the effects of three common comorbid conditions on work and response to vocational rehabilitation, including cognitive impairment, substance abuse, and medical conditions, followed by research on vocational rehabilitation. We then present the results of a randomized controlled trial evaluating the effects of adding cognitive remediation to a vocational rehabilitation program compared with vocational rehabilitation alone in 34 consumers with severe mental illness. Consumers who received both cognitive remediation and vocational rehabilitation demonstrated significantly greater improvements on a cognitive battery over 3 months than those who received vocational rehabilitation alone and had better work outcomes over the 2-year follow-up period. Substance abuse was associated with worse employment outcomes, but did not interact with treatment group, whereas medical comorbidity was not related to work outcomes. More research is warranted to evaluate the interactions between substance abuse and medical comorbidity with vocational rehabilitation and cognitive remediation. PMID:19269925

  6. Prophylactic Azithromycin Therapy After Lung Transplantation: Post hoc Analysis of a Randomized Controlled Trial.

    PubMed

    Ruttens, D; Verleden, S E; Vandermeulen, E; Bellon, H; Vanaudenaerde, B M; Somers, J; Schoonis, A; Schaevers, V; Van Raemdonck, D E; Neyrinck, A; Dupont, L J; Yserbyt, J; Verleden, G M; Vos, R

    2016-01-01

    Prophylactic azithromycin treatment has been demonstrated to improve freedom from bronchiolitis obliterans syndrome (BOS) 2 years after lung transplantation (LTx). In the current study, we re-evaluated the long-term effects of this prophylactic approach in view of the updated classification system for chronic lung allograft dysfunction (CLAD). A retrospective, intention-to-treat analysis of a randomized controlled trial comparing prophylactic treatment with placebo (n = 43) versus azithromycin (n = 40) after LTx was performed. Graft dysfunction (CLAD), graft loss (retransplantation, mortality), evolution of pulmonary function and functional exercise capacity were analyzed 7 years after inclusion of the last study subject. Following LTx, 22/43 (51%) patients of the placebo group and 11/40 (28%) patients of the azithromycin group ever developed CLAD (p = 0.043). CLAD-free survival was significantly longer in the azithromycin group (p = 0.024). No difference was present in proportion of obstructive versus restrictive CLAD between both groups. Graft loss was similar in both groups: 23/43 (53%) versus 16/40 (40%) patients (p = 0.27). Long-term pulmonary function and functional exercise capacity were significantly better in the azithromycin group (p < 0.05). Prophylactic azithromycin therapy reduces long-term CLAD prevalence and improves CLAD-free survival, pulmonary function, and functional exercise capacity after LTx. PMID:26372728

  7. Intervention Effects on Adolescent Physical Activity in the Multicomponent SPACE Study: A Cluster Randomized Controlled Trial

    PubMed Central

    Toftager, Mette; Christiansen, Lars B.; Ersbøll, Annette K.; Kristensen, Peter L.; Due, Pernille; Troelsen, Jens

    2014-01-01

    Background Multicomponent school-based interventions have the potential to reduce the age-related decline in adolescents' physical activity (PA), yet there is not consistent evidence to guide non-curricular and school environment interventions. The aim of this study was to assess the effectiveness of a multicomponent environmental school-based intervention, designed to reduce the age-related decline in PA among adolescents. Methods A cluster randomized controlled trial was conducted with 7 intervention and 7 control schools. Baseline measurements were carried out in spring 2010 with 2 years of follow-up. A total of 1,348 students (11–13 years, in grade 5 and 6) enrolled in the study at baseline. The 14 schools included in the study were located in the Region of Southern Denmark. The intervention consisted of organizational and physical changes in the school environment with a total of 11 intervention components. The primary outcome measure was overall PA (cpm, counts per minute) and was supported by analyses of time spent in MVPA, and time spent sedentary. Furthermore, a secondary outcome measure was PA in school time and during recess. PA was measured using accelerometer (Actigraph GT3X). Results A total of 797 students completed the trial and had valid accelerometer data. No significant difference was found for overall PA with an adjusted difference of −19.1 cpm (95% CI: −93, 53) or for school time activity with an adjusted difference of 6 cpm (95% CI: −73, 85). A sensitivity analysis revealed a positive significant intervention effect of PA in recess with an adjusted difference of 95 cpm. Conclusions No evidence was found of the overall effect of a non-curricular multicomponent school-based intervention on PA among Danish adolescents. The intervention was positively associated with PA during school time and recess, however, with small estimates. Lack of effect on overall PA could be due to both program theory and different degrees of implementation

  8. A Multisite Randomized Effectiveness Trial of Motivational Enhancement Therapy for Spanish-Speaking Substance Users

    ERIC Educational Resources Information Center

    Carroll, Kathleen M.; Martino, Steve; Ball, Samuel A.; Nich, Charla; Frankforter, Tami; Anez, Luis M.; Paris, Manuel; Suarez-Morales, Lourdes; Szapocznik, Jose; Miller, William R.; Rosa, Carmen; Matthews, Julie; Farentinos, Chris

    2009-01-01

    Hispanic individuals are underrepresented in clinical and research populations and are often excluded from clinical trials in the United States. Hence, there are few data on the effectiveness of most empirically validated therapies for Hispanic substance users. The authors conducted a multisite randomized trial comparing the effectiveness of 3…

  9. A brief history of the randomized controlled trial. From oranges and lemons to the gold standard.

    PubMed

    Meldrum, M L

    2000-08-01

    This article discusses the history and development of randomized clinical trial methodology, the reasons for its status and authority as a method of therapeutic evaluation, and the continuing role of clinical judgement in designing, interpreting, and applying the findings of trials. PMID:10949771

  10. Randomized Controlled Trial of Transdermal Secretin on Behavior of Children with Autism

    ERIC Educational Resources Information Center

    Ratliff-Schaub, Karen; Carey, Tracy; Reeves, Gretchen; Rogers, Mary

    2005-01-01

    Previous trials of secretin for the treatment of autism have utilized a single or double dose administered intravenously. This is a report of a double-blind, randomized, controlled crossover trial of transdermally applied secretin in 15 children diagnosed with autism or pervasive developmental delay. Secretin or placebo was applied daily, in…

  11. EEG Neurofeedback for ADHD: Double-Blind Sham-Controlled Randomized Pilot Feasibility Trial

    ERIC Educational Resources Information Center

    Arnold, L. Eugene; Lofthouse, Nicholas; Hersch, Sarah; Pan, Xueliang; Hurt, Elizabeth; Bates, Bethany; Kassouf, Kathleen; Moone, Stacey; Grantier, Cara

    2013-01-01

    Objective: Preparing for a definitive randomized clinical trial (RCT) of neurofeedback (NF) for ADHD, this pilot trial explored feasibility of a double-blind, sham-controlled design and adherence/palatability/relative effect of two versus three treatments/week. Method: Unmedicated 6- to 12-year-olds with "Diagnostic and Statistical Manual of…

  12. Covariate Adjustment Strategy Increases Power in the Randomized Controlled Trial With Discrete-Time Survival Endpoints

    ERIC Educational Resources Information Center

    Safarkhani, Maryam; Moerbeek, Mirjam

    2013-01-01

    In a randomized controlled trial, a decision needs to be made about the total number of subjects for adequate statistical power. One way to increase the power of a trial is by including a predictive covariate in the model. In this article, the effects of various covariate adjustment strategies on increasing the power is studied for discrete-time…

  13. Aerobic and Combined Exercise Sessions Reduce Glucose Variability in Type 2 Diabetes: Crossover Randomized Trial

    PubMed Central

    Figueira, Franciele R.; Umpierre, Daniel; Casali, Karina R.; Tetelbom, Pedro S.; Henn, Nicoli T.; Schaan, Beatriz D.

    2013-01-01

    Purpose To evaluate the effects of aerobic (AER) or aerobic plus resistance exercise (COMB) sessions on glucose levels and glucose variability in patients with type 2 diabetes. Additionally, we assessed conventional and non-conventional methods to analyze glucose variability derived from multiple measurements performed with continuous glucose monitoring system (CGMS). Methods Fourteen patients with type 2 diabetes (56±2 years) wore a CGMS during 3 days. Participants randomly performed AER and COMB sessions, both in the morning (24 h after CGMS placement), and at least 7 days apart. Glucose variability was evaluated by glucose standard deviation, glucose variance, mean amplitude of glycemic excursions (MAGE), and glucose coefficient of variation (conventional methods) as well as by spectral and symbolic analysis (non-conventional methods). Results Baseline fasting glycemia was 139±05 mg/dL and HbA1c 7.9±0.7%. Glucose levels decreased immediately after AER and COMB protocols by ∼16%, which was sustained for approximately 3 hours. Comparing the two exercise modalities, responses over a 24-h period after the sessions were similar for glucose levels, glucose variance and glucose coefficient of variation. In the symbolic analysis, increases in 0 V pattern (COMB, 67.0±7.1 vs. 76.0±6.3, P = 0.003) and decreases in 1 V pattern (COMB, 29.1±5.3 vs. 21.5±5.1, P = 0.004) were observed only after the COMB session. Conclusions Both AER and COMB exercise modalities reduce glucose levels similarly for a short period of time. The use of non-conventional analysis indicates reduction of glucose variability after a single session of combined exercises. Trial Registration Aerobic training, aerobic-resistance training and glucose profile (CGMS) in type 2 diabetes (CGMS exercise). ClinicalTrials.gov ID: NCT00887094. PMID:23536769

  14. A Multicenter, Single-Blind Randomized, Controlled Study of a Volumizing Hyaluronic Acid Filler for Midface Volume Deficit: Patient-Reported Outcomes at 2 Years

    PubMed Central

    Few, Julius; Cox, Sue Ellen; Paradkar-Mitragotri, Deepali; Murphy, Diane K.

    2015-01-01

    Background Juvéderm Voluma XC is a volumizing hyaluronic acid filler used for correction of age-related midface volume deficit (MVD). Objectives The effectiveness of Juvéderm Voluma XC was examined from the patient perspective. Methods Patients with moderate to severe age-related MVD (N = 235) received Juvéderm Voluma XC. At quarterly follow-up visits for 2 years, patients rated treatment outcomes on the Global Aesthetic Improvement Scale (GAIS), overall satisfaction with facial appearance, satisfaction with midfacial regions, achievement of treatment goal, Look and Feel of the Midface (LAFM), and Self-Perception of Age (SPA). Patients recorded treatment-site responses in 30-day diaries. Results At 6 months and 2 years after treatment, 92.8% and 79.0% of patients, respectively, rated their cheek volume as improved/much improved on the GAIS. Improvement in satisfaction with facial appearance was noted by 89.8% of patients at 6 months and 75.8% at 2 years. Increased satisfaction with outer and lower cheek areas and cheek-bone projection and clinically significant improvements in LAFM were noted through month 24. Treatment goals were achieved by 67.8% of patients at 6 months and 49.0% at 2 years. Patients reported looking, on average, 5 years younger at 6 months and 3 years younger at 2 years. The most common treatment site responses were tenderness, swelling, firmness, and lumps/bumps; most were mild to moderate in severity and lasted ≤2 weeks. Conclusions Juvéderm Voluma XC for age-related MVD is effective and well-tolerated from the patient perspective, with results lasting up to 2 years. Level of Evidence 4 Therapeutic PMID:25964628

  15. Multilevel Analysis Methods for Partially Nested Cluster Randomized Trials

    ERIC Educational Resources Information Center

    Sanders, Elizabeth A.

    2011-01-01

    This paper explores multilevel modeling approaches for 2-group randomized experiments in which a treatment condition involving clusters of individuals is compared to a control condition involving only ungrouped individuals, otherwise known as partially nested cluster randomized designs (PNCRTs). Strategies for comparing groups from a PNCRT in the…

  16. Is fresh frozen plasma clinically effective? A systematic review of randomized controlled trials.

    PubMed

    Stanworth, S J; Brunskill, S J; Hyde, C J; McClelland, D B L; Murphy, M F

    2004-07-01

    Summary Randomized controlled trials of good quality are a recognized means to robustly assess the efficacy of interventions in clinical practice. A systematic identification and appraisal of all randomized trials involving fresh frozen plasma (FFP) has been undertaken in parallel to the drafting of the updated British Committee for Standards in Haematology guidelines on the use of FFP. A total of 57 trials met the criteria for inclusion in the review. Most clinical uses of FFP, currently recommended by practice guidelines, are not supported by evidence from randomized trials. In particular, there is little evidence for the effectiveness of the prophylactic use of FFP. Many published trials on the use of FFP have enrolled small numbers of patients, and provided inadequate information on the ability of the trial to detect meaningful differences in outcomes between the two patient groups. Other concerns about the design of the trials include the dose of FFP used, and the potential for bias. No studies have taken adequate account of the extent to which adverse effects might negate the clinical benefits of treatment with FFP. There is a need to consider how best to develop new trials to determine the efficacy of FFP in different clinical scenarios to provide the evidence base to support national guidelines for transfusion practice. Trials of modified FFP (e.g. pathogen inactivated) are of questionable value when there is little evidence that the standard product is an effective treatment. PMID:15198745

  17. Transfusion of fresh frozen plasma in non-bleeding ICU patients -TOPIC TRIAL: study protocol for a randomized controlled trial

    PubMed Central

    2011-01-01

    Background Fresh frozen plasma (FFP) is an effective therapy to correct for a deficiency of multiple coagulation factors during bleeding. In past years, use of FFP has increased, in particular in patients on the Intensive Care Unit (ICU), and has expanded to include prophylactic use in patients with a coagulopathy prior to undergoing an invasive procedure. Retrospective studies suggest that prophylactic use of FFP does not prevent bleeding, but carries the risk of transfusion-related morbidity. However, up to 50% of FFP is administered to non-bleeding ICU patients. With the aim to investigate whether prophylactic FFP transfusions to critically ill patients can be safely omitted, a multi-center randomized clinical trial is conducted in ICU patients with a coagulopathy undergoing an invasive procedure. Methods A non-inferiority, prospective, multicenter randomized open-label, blinded end point evaluation (PROBE) trial. In the intervention group, a prophylactic transfusion of FFP prior to an invasive procedure is omitted compared to transfusion of a fixed dose of 12 ml/kg in the control group. Primary outcome measure is relevant bleeding. Secondary outcome measures are minor bleeding, correction of International Normalized Ratio, onset of acute lung injury, length of ventilation days and length of Intensive Care Unit stay. Discussion The Transfusion of Fresh Frozen Plasma in non-bleeding ICU patients (TOPIC) trial is the first multi-center randomized controlled trial powered to investigate whether it is safe to withhold FFP transfusion to coagulopathic critically ill patients undergoing an invasive procedure. Trial Registration Trial registration: Dutch Trial Register NTR2262 and ClinicalTrials.gov: NCT01143909 PMID:22196464

  18. Randomized controlled trials in relapsed/refractory follicular lymphoma: a systematic review and meta-analysis.

    PubMed

    Police, Rachel L; Trask, Peter C; Wang, Jianmin; Olivares, Robert; Khan, Shahnaz; Abbe, Adeline; Colosia, Ann; Njue, Annete; Sherril, Beth; Ruiz-Soto, Rodrigo; Kaye, James A; Hamadani, Mehdi

    2016-10-01

    This systematic literature review evaluated the clinical efficacy and safety of interventions used in relapsed/refractory follicular lymphoma. Primary efficacy outcomes were objective response rate, progression-free survival and overall survival. Safety endpoints were grade 3/4 toxicities, serious adverse events and withdrawals or deaths due to toxicity. Studies were selected if they were randomized controlled trials reporting on the efficacy or safety of treatments for relapsed or refractory follicular lymphoma, and if outcomes were reported separately from trials that included other lymphoid neoplasms. We used the Bucher method for conducting adjusted indirect comparisons within a meta-analysis. We identified 10 randomized controlled trials of treatments for relapsed/refractory follicular lymphoma. The most prominent drug investigated (alone or in combination) was rituximab. Most trials did not report median overall survival. Two trials reported median event-free survival (range, 1.2-23.2 months). Six of ten trials reported objective response rate (range, 9-93%). Meta-analysis showed only one statistically significant result: rituximab + bortezomib yielded a significantly higher objective response rate than rituximab monotherapy (relative risk, 1.28; 95% confidence interval, 1.11-1.47). Otherwise, there were no discernable differences in overall survival or progression-free survival, partly due to insufficient reporting of results in the clinical trials. The relatively small number of randomized controlled trials, few overlapping treatment arms, and variability in the randomized controlled trial features and in the endpoints studied complicate the formal comparison of therapies for relapsed/refractory follicular lymphoma. Additional well-designed randomized controlled trials are needed to fully understand the relative outcomes of older and more recently developed therapies. PMID:26320127

  19. Efficacy of Bosentan in patients after Fontan procedures: a double-blind, randomized controlled trial.

    PubMed

    Shang, Xiao-Ke; Lu, Rong; Zhang, Xi; Zhang, Chang-Dong; Xiao, Shu-Na; Liu, Mei; Wang, Bin; Dong, Nian-Guo

    2016-08-01

    Fontan surgery is a widely used palliative procedure that significantly improves the survival period of patients with complex congenital heart disease (CHD). However, it does not decrease postoperative complication rate. Previous studies suggested that elevated mean pulmonary artery pressure (mPAP) and vascular resistance lead to decreased exercise tolerance and myocardial dysfunction. Therapy with endothelial receptor antagonists (Bosentan) has been demonstrated to improve the patients' prognosis. A double-blind, randomized controlled trial was performed to explore the efficacy of Bosentan in treating patients who underwent the Fontan procedure. Eligible participants were randomly divided into Bosentan group and control group. Liver function was tested at a local hospital and the results were reported to the phone inspector every month. If the results suggested abnormal liver function, treatment would be adjusted or terminated. All the participants finished the follow-up study, with no patients lost to follow-up. Unblinding after 2-year follow-up, no mortality was observed in either group. However, secondary end-points were found to be significantly different in the comparable groups. The cardiac function and 6-min walking distance in the Bosentan group were significantly superior to those in the control group (P=0.018 and P=0.027). Bosentan could improve New York Heart Association (NYHA) functional status and improve the results of the 6-min walking test (6MWT) in Fontan patients post-surgery, and no other benefits were observed. Furthermore, a primary meta-analysis study systematically reviewed all the similar clinical trails worldwide and concluded an overall NYHA class improvement in Fontan patients who received Bosentan treatments. PMID:27465329

  20. Bifidobacterium lactis in Treatment of Children with Acute Diarrhea. A Randomized Double Blind Controlled Trial

    PubMed Central

    El-Soud, Neveen Helmy Abou; Said, Reem Nabil; Mosallam, Dalia Sayed; Barakat, Nahla Abdel Moniem; Sabry, Mohamed Ahmed

    2015-01-01

    BACKGROUND: Probiotics are becoming increasingly popular treatment for children diarrhea. Although there are several probiotic strains potentially useful, researches were often limited to certain strains. AIM: To test Bifidobacterium lactis on morbidity of acute diarrhea in children less than 2 years. SUBJECTS AND METHODS: A randomized double-blind controlled clinical trial was conducted in 50 children (1 - 23 months) admitted with acute diarrhea to the Pediatric Hospital, Cairo University and were randomly assigned to receive in addition to usual treatment of diarrhea according to WHO guidelines; one of two treatments either milk formula non-supplemented (n = 25) or supplemented (n = 25) with Bifidobacterium lactis 14.5 × 106 CFU/100 ml daily for one week. Primary outcomes were frequency and duration of diarrhea and hospital stay. Secondary outcomes were duration of fever and vomiting episodes. Safety and tolerance were also recorded. RESULTS: On admission, patients’ characteristics of both groups (50 cases) were similar. For children who received the probiotics for one week; mean duration of diarrhoea was shorter than in controls (3.12 ± 0.92 vs. 4.10 ± 0.94 days) (P = 0.02), number of motions per day was less than in controls (3.96 ± 0.62 vs. 4.46 ± 0.85) (P = 0.04) and discharge from hospital <2 days was more frequent than in controls (72% vs. 44%) (P = 0.048). There was no effect on fever (P = 0.63) or vomiting (P = 0.54). CONCLUSION: Bifidobacterium lactis probiotics in supplemented milk formula decreased significantly frequency, duration of diarrhea, and hospital stay than usual treatment alone in children with acute diarrhea. Additional researches on other uncommon local probiotic species should be encouraged. PMID:27275258

  1. Prevention of Bone Loss with Risedronate in Breast Cancer Survivors: A Randomized, Controlled Clinical Trial

    PubMed Central

    Greenspan, Susan L.; Vujevich, Karen T.; Brufsky, Adam; Lembersky, Barry C.; van Londen, G.J.; Jankowitz, Rachel C.; Puhalla, Shannon L.; Rastogi, Priya; Perera, Subashan

    2016-01-01

    Purpose Aromatase inhibitors (AIs), adjuvant endocrine therapy for postmenopausal women with hormone receptor positive breast cancer, are associated with bone loss and fractures. Our objectives were to determine if 1) oral bisphosphonate therapy can prevent bone loss in women on an AI and, 2) early changes in bone turnover markers (BTM) can predict later changes in bone mineral density (BMD). Methods We conducted a 2 year double-blind, placebo-controlled, randomized trial in 109 postmenopausal women with low bone mass on an aromatase inhibitor (AI-anastrozole, letrozole, or exemestane) for hormone receptor positive breast cancer. Participants were randomized to once weekly risedronate 35 mg or placebo and all received calcium plus vitamin D. The main outcome measures included BMD, BTM [carboxy-terminal collagen crosslinks (CTX) and N-terminal propeptide of type 1 procollagen (P1NP)] and safety. Results Eighty-seven percent completed 24 months. BMD increased more in the active treatment group compared to placebo with an adjusted difference at 24 months of 3.9 ± 0.7 percentage points at the spine and 3.2 ± 0.5 percentage points at the hip (both p<0.05). The adjusted difference between the active treatment and placebo groups were 0.09 ± 0.04 nmol/LBCE for CTX and 23.3 ± 4.8 µg/mL for P1NP (both p<0.05). Women with greater 12-month decreases in CTX and P1NP in the active treatment group had a greater 24-month increase in spinal BMD (p<0.05). The oral therapy was safe and well tolerated. Conclusion In postmenopausal women with low bone mass and breast cancer on an AI, the oral bisphosphonate risedronate maintained skeletal health. PMID:25792492

  2. A Randomized Controlled Trial of Allopurinol in Patients With Peripheral Arterial Disease

    PubMed Central

    Robertson, Alan J.; Struthers, Allan D.

    2016-01-01

    Background Patients with peripheral arterial disease (PAD) are limited by intermittent claudication in the distance they can walk. Allopurinol has been shown in coronary arterial disease to prolong exercise before angina occurs, likely by prevention of oxygen wastage in tissues and reduction of harmful oxidative stress. Methods In this study we evaluated whether allopurinol could prolong the time to development of leg pain in participants with PAD. In a double-blind, randomized controlled clinical trial participants were randomized to receive either allopurinol 300 mg twice daily or placebo for 6 months. The primary outcome was change in exercise capacity on treadmill testing at 6 months. Secondary outcomes were 6-minute walking distance, Walking Impairment Questionnaire, SF-36 questionnaire, flow-mediated dilatation, and oxidized low-density lipoprotein. Outcome measures were repeated midstudy and at the end of study. The mean age of the 50 participants was 68.4 ± 1.2 years with 39 of 50 (78%) male. Results Five participants withdrew during the study (2 active, 3 placebo). There was a significant reduction in uric acid levels in those who received active treatment of 52.1% (P < 0.001), but no significant change in either the pain-free or the maximum walking distance. Other measures of exercise capacity, blood vessel function, and the participants' own assessment of their health and walking ability also did not change during the course of the study. Conclusions Although allopurinol has been shown to be of benefit in a number of other diseases, in this study there was no evidence of any improvement after treatment in patients with PAD. PMID:26277090

  3. Mast Cell Stabilizer (Ketotifen) in Fibromyalgia: Phase 1 Randomized Controlled Clinical Trial

    PubMed Central

    Ang, Dennis C.; Hilligoss, Janna; Stump, Timothy

    2014-01-01

    Objectives Compared to healthy controls, patients with fibromyalgia (FM) have more mast cells in the skin. Whether mast cells are involved in the pathogenesis of FM is unclear. We sought to determine the effects of a mast cell stabilizer (ketotifen) on FM symptoms. Methods Fifty-one FM subjects were randomized to daily oral ketotifen 2 mg BID (n=24) for 8 weeks or placebo (N=27). Mean age of subjects was 51.2 years (standard deviation/SD 8.4); 88% were female and 88% were white; 22% were taking concomitant opiates; and mean pressure pain sensitivity (range 0-20) was 10.0 (0.4). At study entry, the weekly average pain intensity was 6.4 (1.1) and the mean score on the Revised Fibromyalgia Impact Questionnaire (FIQR) was 66.8 (14.0). Results We found no statistically significant treatment group differences from baseline in either group for the two primary measures: weekly average pain intensity [ketotifen −1.3 (1.9) vs. placebo −1.5 (1.9), p=0.7]; and FIQR score [−12.1 (19.5) vs. −12.2 (18.1), p=0.9]. No secondary outcome measures (BPI pain intensity, and pressure pain sensitivity) reached statistical significance; results did not differ in the intent-to-treat and completer analyses. Other than transient sedation [6 (28.6%) vs. 1 (4.0%)], ketotifen was well tolerated. Discussion The study results question whether skin mast cells play a major role in the pathogenesis of FM. However, given the role of mast cells in peripheral and central nociception, and the minimal side effects of ketotifen, a randomized clinical trial using increasing doses of ketotifen may be warranted. PMID:25370135

  4. A Group-Based Yoga Therapy Intervention for Urinary Incontinence in Women: A Pilot Randomized Trial

    PubMed Central

    Huang, Alison J.; Jenny, Hillary E.; Chesney, Margaret A.; Schembri, Michael; Subak, Leslee L.

    2015-01-01

    Objective To examine the feasibility, efficacy, and safety of a group-based yoga therapy intervention for middle-aged and older women with urinary incontinence. Methods We conducted a pilot randomized trial of ambulatory women aged 40 years and older with stress, urgency, or mixed-type incontinence. Women were randomized to a 6-week yoga therapy program (N=10) consisting of twice weekly group classes and once weekly home practice or a waitlist control group (N=9). All participants also received written pamphlets about standard behavioral self-management strategies for incontinence. Changes in incontinence were assessed by 7-day voiding diaries. Results Mean (±SD) age was 61.4 (±8.2) years, and mean baseline frequency of incontinence was 2.5 (±1.3) episodes/day. After 6 weeks, total incontinence frequency decreased by 66% (1.8 [±0.9] fewer episodes/day) in the yoga therapy versus 13% (0.3 [±1.7] fewer episodes/day) in the control group (P=0.049). Participants in the yoga therapy group also reported an average 85% decrease in stress incontinence frequency (0.7 [±0.8] fewer episodes/day) compared to a 25% increase in controls (0.2 [± 1.1] more episodes/day) (P=0.039). No significant differences in reduction in urgency incontinence were detected between the yoga therapy versus control groups (1.0 [±1.0] versus 0.5 [±0.5] fewer episodes/day, P=0.20). All women starting the yoga therapy program completed at least 90% of group classes and practice sessions. Two participants in each group reported adverse events unrelated to the intervention. Conclusions Findings provide preliminary evidence to support the feasibility, efficacy, and safety of a group-based yoga therapy intervention to improve urinary incontinence in women. PMID:24763156

  5. Randomized trial in malignant biliary obstruction: Plastic vs partially covered metal stents

    PubMed Central

    Moses, Peter L; AlNaamani, Khalid M; Barkun, Alan N; Gordon, Stuart R; Mitty, Roger D; Branch, M Stanley; Kowalski, Thomas E; Martel, Myriam; Adam, Viviane

    2013-01-01

    AIM: To compare efficacy and complications of partially covered self-expandable metal stent (pcSEMS) to plastic stent (PS) in patients treated for malignant, infrahilar biliary obstruction. METHODS: Multicenter prospective randomized clinical trial with treatment allocation to a pcWallstent® (SEMS) or a 10 French PS. Palliative patients aged ≥ 18, for infrahilar malignant biliary obstruction and a Karnofsky performance scale index > 60% from 6 participating North American university centers. Primary endpoint was time to stent failure, with secondary outcomes of death, adverse events, Karnofsky performance score and short-form-36 scale administered on a three-monthly basis for up to 2 years. Survival analyses were performed for stent failure and death, with Cox proportional hazards regression models to determine significant predictive characteristics. RESULTS: Eighty-five patients were accrued over 37 mo, 42 were randomized to the SEMS group and 83 patients were available for analyses. Time to stent failure was 385.3 ± 52.5 d in the SEMS and 153.3 ± 19.8 d in the PS group, P = 0.006. Time to death did not differ between groups (192.3 ± 23.4 d for SEMS vs 211.5 ± 28.0 d for PS, P = 0.70). The only significant predictor was treatment allocation, relating to the time to stent failure (P = 0.01). Amongst other measured outcomes, only cholangitis differed, being more common in the PS group (4.9% vs 24.5%, P = 0.029). The small number of patients in follow-up limits longitudinal assessments of performance and quality of life. From an initially planned 120 patients, only 85 patients were recruited. CONCLUSION: Partially covered SEMS result in a longer duration till stent failure without increased complication rates, yet without accompanying measurable benefits in survival, performance, or quality of life. PMID:24379581

  6. Balancing Contamination and Referral Bias in a Randomized Clinical Trial: An Application of Pseudo-Cluster Randomization.

    PubMed

    Pence, Brian W; Gaynes, Bradley N; Thielman, Nathan M; Heine, Amy; Mugavero, Michael J; Turner, Elizabeth L; Quinlivan, Evelyn B

    2015-12-15

    In randomized trials of provider-focused clinical interventions, treatment allocation often cannot be blinded to participants, study staff, or providers. The choice of unit of randomization (patient, provider, or clinic) entails tradeoffs in cost, power, and bias. Provider- or clinic-level randomization can minimize contamination, but it incurs the equally problematic potential for referral bias; that is, because arm assignment of future participants generally cannot be concealed, differences between arms may arise in the types of patients enrolled. Pseudo-cluster randomization is a novel study design that balances these competing validity threats. Providers are randomly assigned to an imbalanced proportion of intervention-arm participants (e.g., 80% or 20%). Providers can be masked to the imbalance, avoiding referral bias. Contamination is reduced because only a minority of control-arm participants are treated by majority-intervention providers. Pseudo-cluster randomization was implemented in a randomized trial of a decision support intervention to manage depression among patients receiving human immunodeficiency virus care in the southern United States in 2010-2014. The design appears successful in avoiding referral bias (participants were comparable between arms on important characteristics) and contamination (key depression treatment indicators were comparable between usual care participants managed by majority-intervention and majority-usual care providers and were markedly different compared with intervention participants). PMID:26628511

  7. The Sonoma Water Evaluation Trial (SWET): A randomized drinking water intervention trial to reduce gastrointestinal illness in older adults

    EPA Science Inventory

    Objectives. We estimate the risk of highly credible gastrointestinal illness (HCGI) among adults 55 and older in a community drinking tap water meeting current U.S. standards. Methods. We conducted a randomized, triple-blinded, crossover trial in 714 households (988 indiv...

  8. From Protocols to Publications: A Study in Selective Reporting of Outcomes in Randomized Trials in Oncology

    PubMed Central

    Raghav, Kanwal Pratap Singh; Mahajan, Sminil; Yao, James C.; Hobbs, Brian P.; Berry, Donald A.; Pentz, Rebecca D.; Tam, Alda; Hong, Waun K.; Ellis, Lee M.; Abbruzzese, James; Overman, Michael J.

    2015-01-01

    Purpose The decision by journals to append protocols to published reports of randomized trials was a landmark event in clinical trial reporting. However, limited information is available on how this initiative effected transparency and selective reporting of clinical trial data. Methods We analyzed 74 oncology-based randomized trials published in Journal of Clinical Oncology, the New England Journal of Medicine, and The Lancet in 2012. To ascertain integrity of reporting, we compared published reports with their respective appended protocols with regard to primary end points, nonprimary end points, unplanned end points, and unplanned analyses. Results A total of 86 primary end points were reported in 74 randomized trials; nine trials had greater than one primary end point. Nine trials (12.2%) had some discrepancy between their planned and published primary end points. A total of 579 nonprimary end points (median, seven per trial) were planned, of which 373 (64.4%; median, five per trial) were reported. A significant positive correlation was found between the number of planned and nonreported nonprimary end points (Spearman r = 0.66; P < .001). Twenty-eight studies (37.8%) reported a total of 65 unplanned end points; 52 (80.0%) of which were not identified as unplanned. Thirty-one (41.9%) and 19 (25.7%) of 74 trials reported a total of 52 unplanned analyses involving primary end points and 33 unplanned analyses involving nonprimary end points, respectively. Studies reported positive unplanned end points and unplanned analyses more frequently than negative outcomes in abstracts (unplanned end points odds ratio, 6.8; P = .002; unplanned analyses odd ratio, 8.4; P = .007). Conclusion Despite public and reviewer access to protocols, selective outcome reporting persists and is a major concern in the reporting of randomized clinical trials. To foster credible evidence-based medicine, additional initiatives are needed to minimize selective reporting. PMID:26304898

  9. Randomized Trial of a Gatekeeper Program for Suicide Prevention: 1-Year Impact on Secondary School Staff

    ERIC Educational Resources Information Center

    Wyman, Peter A.; Brown, C. Hendricks; Inman, Jeff; Cross, Wendi; Schmeelk-Cone, Karen; Guo, Jing; Pena, Juan B.

    2008-01-01

    Gatekeeper-training programs, designed to increase identification and referral of suicidal individuals, are widespread but largely untested. A group-based randomized trial with 32 schools examined impact of Question, Persuade, Refer (QPR) training on a stratified random sample of 249 staff with 1-year average follow-up. To test QPR impact, the…

  10. Effect of Art Production on Negative Mood: A Randomized, Controlled Trial

    ERIC Educational Resources Information Center

    Bell, Chloe E.; Robbins, Steven J.

    2007-01-01

    Art therapists have long held that art production causes reductions in stress and elevations in mood (Rubin, 1999). The authors examined this claim in a randomized, controlled trial. Fifty adults between the ages of 18 and 30 were randomly assigned to either create an art work or to view and sort a series of art prints. Three measures of overall…

  11. The Late Pretest Problem in Randomized Control Trials of Education Interventions. NCEE 2009-4033

    ERIC Educational Resources Information Center

    Schochet, Peter Z.

    2008-01-01

    Pretest-posttest experimental designs are often used in randomized control trials (RCTs) in the education field to improve the precision of the estimated treatment effects. For logistic reasons, however, pretest data are often collected after random assignment, so that including them in the analysis could bias the posttest impact estimates. Thus,…

  12. The Late Pretest Problem in Randomized Control Trials of Education Interventions

    ERIC Educational Resources Information Center

    Schochet, Peter Z.

    2010-01-01

    Pretest-posttest experimental designs often are used in randomized control trials (RCTs) in the education field to improve the precision of the estimated treatment effects. For logistic reasons, however, pretest data often are collected after random assignment, so that including them in the analysis could bias the posttest impact estimates. Thus,…

  13. Intraclass Correlations for Three-Level Multi-Site Cluster-Randomized Trials of Science Achievement

    ERIC Educational Resources Information Center

    Westine, Carl D.

    2015-01-01

    A cluster-randomized trial (CRT) relies on random assignment of intact clusters to treatment conditions, such as classrooms or schools (Raudenbush & Bryk, 2002). One specific type of CRT, a multi-site CRT (MSCRT), is commonly employed in educational research and evaluation studies (Spybrook & Raudenbush, 2009; Spybrook, 2014; Bloom,…

  14. What to Do when Data Are Missing in Group Randomized Controlled Trials. NCEE 2009-0049

    ERIC Educational Resources Information Center

    Puma, Michael J.; Olsen, Robert B.; Bell, Stephen H.; Price, Cristofer

    2009-01-01

    This NCEE Technical Methods report examines how to address the problem of missing data in the analysis of data in Randomized Controlled Trials (RCTs) of educational interventions, with a particular focus on the common educational situation in which groups of students such as entire classrooms or schools are randomized. Missing outcome data are a…

  15. Outcomes from a School-Randomized Controlled Trial of Steps to Respect: A Bullying Prevention Program

    ERIC Educational Resources Information Center

    Brown, Eric C.; Low, Sabina; Smith, Brian H.; Haggerty, Kevin P.

    2011-01-01

    This study reports the outcomes of a randomized controlled trial of Steps to Respect: A Bullying Prevention Program conducted in 33 California elementary schools. Schools were matched on school demographic characteristics and assigned randomly to intervention or waitlisted control conditions. Outcome measures were obtained from (a) all school…

  16. Brief Motivational Interventions for Heavy College Drinkers: A Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Carey, Kate B.; Carey, Michael P.; Maisto, Stephen A.; Henson, James H.

    2006-01-01

    In this randomized controlled trial, the authors evaluated brief motivational interventions (BMIs) for at-risk college drinkers. Heavy drinking students (N = 509; 65% women, 35% men) were randomized into 1 of 6 intervention conditions formed by crossing the baseline Timeline Followback (TLFB) interview (present versus absent) and intervention type…

  17. A Randomized Controlled Trial of a Standardized Behavior Management Intervention for Students with Externalizing Behavior

    ERIC Educational Resources Information Center

    Forster, Martin; Sundell, Knut; Morris, Richard J.; Karlberg, Martin; Melin, Lennart

    2012-01-01

    This study reports the results from a Swedish randomized controlled trial of a standardized behavior management intervention. The intervention targeted students with externalizing behavior in a regular education setting. First- and second-grade students (N = 100) from 38 schools were randomly assigned to either the intervention or an active…

  18. Meta-Analysis of Randomized, Controlled Treatment Trials for Pediatric Obsessive-Compulsive Disorder

    ERIC Educational Resources Information Center

    Watson, Hunna J.; Rees, Clare S.

    2008-01-01

    Objective: To conduct a meta-analysis on randomized, controlled treatment trials of pediatric obsessive-compulsive disorder (OCD). Method: Studies were included if they employed randomized, controlled methodology and treated young people (19 years or under) with OCD. A comprehensive literature search identified 13 RCTs containing 10…

  19. Maternal Dietary Counseling Reduces Consumption of Energy-Dense Foods among Infants: A Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Vitolo, Marcia Regina; Bortolini, Gisele Ane; Campagnolo, Paula Dal Bo; Hoffman, Daniel J.

    2012-01-01

    Objective: To evaluate the impact of a dietary counseling in reducing the intake of energy-dense foods by infants. Design: A randomized controlled trial. Setting and Participants: Sao Leopoldo, Brazil. Mothers and infants of a low-income-group population were randomized into intervention (n = 163) and received dietary counseling during 10 home…

  20. Randomized Controlled Trial of a Preventive Intervention for Perinatal Depression in High-Risk Latinas

    ERIC Educational Resources Information Center

    Le, Huynh-Nhu; Perry, Deborah F.; Stuart, Elizabeth A.

    2011-01-01

    Objective: A randomized controlled trial was conducted to evaluate the efficacy of a cognitive-behavioral (CBT) intervention to prevent perinatal depression in high-risk Latinas. Method: A sample of 217 participants, predominantly low-income Central American immigrants who met demographic and depression risk criteria, were randomized into usual…

  1. A Parent-Adolescent Intervention to Increase Sexual Risk Communication: Results of a Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Villarruel, Antonia M.; Cherry, Carol Loveland; Cabriales, Esther Gallegos; Ronis, David L.; Zhou, Yan

    2008-01-01

    This article reports results of a randomized controlled trial designed to test an intervention to increase parent-adolescent sexual risk communication among Mexican parents. Data were analyzed from parents (n = 791) randomly assigned to an HIV risk reduction or health promotion intervention. Measures were administered at pretest, posttest, and 6-…

  2. Effects of Check and Connect on Attendance, Behavior, and Academics: A Randomized Effectiveness Trial

    ERIC Educational Resources Information Center

    Maynard, Brandy R.; Kjellstrand, Elizabeth K.; Thompson, Aaron M.

    2014-01-01

    Objectives: This study examined the effects of Check & Connect (C&C) on the attendance, behavior, and academic outcomes of at-risk youth in a field-based effectiveness trial. Method: A multisite randomized block design was used, wherein 260 primarily Hispanic (89%) and economically disadvantaged (74%) students were randomized to treatment…

  3. After-School Multifamily Groups: A Randomized Controlled Trial Involving Low-Income, Urban, Latino Children

    ERIC Educational Resources Information Center

    McDonald, Lynn; Moberg, D. Paul; Brown, Roger; Rodriguez-Espiricueta, Ismael; Flores, Nydia I.; Burke, Melissa P.; Coover, Gail

    2006-01-01

    This randomized controlled trial evaluated a culturally representative parent engagement strategy with Latino parents of elementary school children. Ten urban schools serving low-income children from mixed cultural backgrounds participated in a large study. Classrooms were randomly assigned either either to an after-school, multifamily support…

  4. Testing a Violence-Prevention Intervention for Incarcerated Women Using a Randomized Control Trial

    ERIC Educational Resources Information Center

    Kubiak, Sheryl Pimlott; Kim, Woo Jong; Fedock, Gina; Bybee, Deborah

    2015-01-01

    Objective: Beyond Violence (BV), a new prevention program for women with assaultive offenses, demonstrated feasibility in previous studies. This study's purpose is to assess the efficacy of BV using a randomized control trial. Method: Eligible women were randomly assigned to treatment as usual (TAU) and the experimental condition (BV). Measures of…

  5. Part versus Whole: A Randomized Trial of Central Venous Catheterization Education

    ERIC Educational Resources Information Center

    Chan, Angela; Singh, Sunita; Dubrowski, Adam; Pratt, Daniel D.; Zalunardo, Nadia; Nair, Parvarthy; McLaughlin, Kevin; Ma, Irene W. Y.

    2015-01-01

    Central venous catheterization (CVC) is a complex but commonly performed procedure. How best to teach this complex skill has not been clearly delineated. We conducted a randomized trial of the effects of two types of teaching of CVC on skill acquisition and retention. We randomly assigned novice internal medicine residents to learning CVC in-part…

  6. Evaluating the Collaborative Strategic Reading Intervention: An Overview of Randomized Controlled Trial Options

    ERIC Educational Resources Information Center

    Hitchcock, John H.; Kurki, Anja; Wilkins, Chuck; Dimino, Joseph; Gersten, Russell

    2009-01-01

    When attempting to determine if an intervention has a causal impact, the "gold standard" of program evaluation is the randomized controlled trial (RCT). In education studies random assignment is rarely feasible at the student level, making RCTs harder to conduct. School-level assignment is more common but this often requires considerable resources…

  7. The Efficacy of Parent-Child Interaction Therapy with Chinese Families: Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Leung, Cynthia; Tsang, Sandra; Sin, Tammy C. S.; Choi, Siu-yan

    2015-01-01

    Objective: This study aimed to examine the efficacy of the Parent-Child Interaction Therapy (PCIT) in Hong Kong Chinese families, using randomized controlled trial design. Methods: The participants included 111 Hong Kong Chinese parents with children aged 2--7 years old, who were randomized into the intervention group (n = 54) and control group (n…

  8. A Data Management System Integrating Web-Based Training and Randomized Trials

    ERIC Educational Resources Information Center

    Muroff, Jordana; Amodeo, Maryann; Larson, Mary Jo; Carey, Margaret; Loftin, Ralph D.

    2011-01-01

    This article describes a data management system (DMS) developed to support a large-scale randomized study of an innovative web-course that was designed to improve substance abuse counselors' knowledge and skills in applying a substance abuse treatment method (i.e., cognitive behavioral therapy; CBT). The randomized trial compared the performance…

  9. Intention-to-Treat Analysis in Partially Nested Randomized Controlled Trials with Real-World Complexity

    ERIC Educational Resources Information Center

    Schweig, Jonathan David; Pane, John F.

    2016-01-01

    Demands for scientific knowledge of what works in educational policy and practice has driven interest in quantitative investigations of educational outcomes, and randomized controlled trials (RCTs) have proliferated under these conditions. In educational settings, even when individuals are randomized, both experimental and control students are…

  10. Understanding Statistical Power in Cluster Randomized Trials: Challenges Posed by Differences in Notation and Terminology

    ERIC Educational Resources Information Center

    Spybrook, Jessaca; Hedges, Larry; Borenstein, Michael

    2014-01-01

    Research designs in which clusters are the unit of randomization are quite common in the social sciences. Given the multilevel nature of these studies, the power analyses for these studies are more complex than in a simple individually randomized trial. Tools are now available to help researchers conduct power analyses for cluster randomized…

  11. Efficacy of the "Responsive Classroom" Approach: Results from a 3-Year, Longitudinal Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Rimm-Kaufman, Sara E.; Larsen, Ross A. A.; Baroody, Alison E.; Curby, Timothy W.; Ko, Michelle; Thomas, Julia B.; Merritt, Eileen G.; Abry, Tashia; DeCoster, Jamie

    2014-01-01

    This randomized controlled field trial examined the efficacy of the Responsive Classroom (RC) approach on student achievement. Schools (n = 24) were randomized into intervention and control conditions; 2,904 children were studied from end of second to fifth grade. Students at schools assigned to the RC condition did not outperform students at…

  12. Two-Year Follow-up of a Randomized Effectiveness Trial Evaluating MST for Juveniles Who Sexually Offend

    PubMed Central

    Letourneau, Elizabeth J.; Henggeler, Scott W.; McCart, Michael R.; Borduin, Charles M.; Schewe, Paul A.; Armstrong, Kevin S.

    2015-01-01

    Objective Building on prior efficacy trials (i.e., university based, graduate students as therapists), the primary purpose of this study was to determine whether favorable 12-month outcomes obtained in a randomized effectiveness trial (i.e., implemented by practitioners in a community mental health center) of multisystemic therapy (MST) with juveniles who had sexually offended (JSO) were sustained through a second year of follow-up. Method JSO (n = 124 male youth) and their families were randomly assigned to MST, which was family based and delivered by community-based practitioners, or to treatment as usual (TAU), which was primarily group-based cognitive-behavioral interventions delivered by professionals within the juvenile justice system. Youth averaged 14.7 (SD = 1.7) years of age at referral, were primarily African American (54%), and 30% were Hispanic. All youth had been diverted or adjudicated for a sexual offense. Analyses examined whether MST effects reported previously at 1-year follow-up for problem sexual behaviors, delinquency, substance use, and out-of-home placement were sustained through a second year of follow-up. In addition, arrest records were examined from baseline through 2-year follow-up. Results During the second year of follow-up, MST treatment effects were sustained for three of four measures of youth problem sexual behavior, self-reported delinquency, and out-of-home placements. The base rate for sexual offense rearrests was too low to conduct statistical analyses, and a between-groups difference did not emerge for other criminal arrests. Conclusions For the most part, the 2-year follow-up findings from this effectiveness study are consistent with favorable MST long-term results with JSO in efficacy research. In contrast with many MST trials, however, decreases in rearrests were not observed. PMID:24188082

  13. Two Years Follow up of Domain Specific Cognitive Training in Relapsing Remitting Multiple Sclerosis: A Randomized Clinical Trial

    PubMed Central

    Mattioli, Flavia; Bellomi, Fabio; Stampatori, Chiara; Provinciali, Leandro; Compagnucci, Laura; Uccelli, Antonio; Pardini, Matteo; Santuccio, Giuseppe; Fregonese, Giuditta; Pattini, Marianna; Allegri, Beatrice; Clerici, Raffaella; Lattuada, Annalisa; Montomoli, Cristina; Corso, Barbara; Gallo, Paolo; Riccardi, Alice; Ghezzi, Angelo; Roscio, Marco; Tola, Maria Rosaria; Calanca, Chiara; Baldini, Daria; Trafficante, Debora; Capra, Ruggero

    2016-01-01

    Cognitive rehabilitation in multiple sclerosis (MS) has been reported to induce neuropsychological improvements, but the persistence of these effects has been scarcely investigated over long follow ups. Here, the results of a multicenter randomized clinical trial are reported, in which the efficacy of 15 week domain specific cognitive training was evaluated at 2 years follow up in 41 patients. Included patients were randomly assigned either to domain specific cognitive rehabilitation, or to aspecific psychological intervention. Patients who still resulted to be cognitively impaired at 1 year follow up were resubmitted to the same treatment, whereas the recovered ones were not. Neuropsychological tests and functional scales were administered at 2 years follow up to all the patients. Results revealed that both at 1 and at 2 years follow up more patients in the aspecific group (18/19, 94% and 13/17, 76% respectively) than in the specific group (11/22, 50% and 5/15, 33% respectively) resulted to be cognitively impaired. Furthermore patients belonging to the specific group showed significantly less impaired tests compared with the aspecific group ones (p = 0.02) and a significant amelioration in the majority of the tests. On the contrary patients in the aspecific group did not change. The specific group subjects also perceived a subjective improvement in their cognitive performance, while the aspecific group patients did not. These results showed that short time domain specific cognitive rehabilitation is a useful treatment for patients with MS, shows very long lasting effects, compared to aspecific psychological interventions. Also subjective cognitive amelioration was found in patients submitted to domain specific treatment after 2 years. PMID:26941630

  14. Two Years Follow up of Domain Specific Cognitive Training in Relapsing Remitting Multiple Sclerosis: A Randomized Clinical Trial.

    PubMed

    Mattioli, Flavia; Bellomi, Fabio; Stampatori, Chiara; Provinciali, Leandro; Compagnucci, Laura; Uccelli, Antonio; Pardini, Matteo; Santuccio, Giuseppe; Fregonese, Giuditta; Pattini, Marianna; Allegri, Beatrice; Clerici, Raffaella; Lattuada, Annalisa; Montomoli, Cristina; Corso, Barbara; Gallo, Paolo; Riccardi, Alice; Ghezzi, Angelo; Roscio, Marco; Tola, Maria Rosaria; Calanca, Chiara; Baldini, Daria; Trafficante, Debora; Capra, Ruggero

    2016-01-01

    Cognitive rehabilitation in multiple sclerosis (MS) has been reported to induce neuropsychological improvements, but the persistence of these effects has been scarcely investigated over long follow ups. Here, the results of a multicenter randomized clinical trial are reported, in which the efficacy of 15 week domain specific cognitive training was evaluated at 2 years follow up in 41 patients. Included patients were randomly assigned either to domain specific cognitive rehabilitation, or to aspecific psychological intervention. Patients who still resulted to be cognitively impaired at 1 year follow up were resubmitted to the same treatment, whereas the recovered ones were not. Neuropsychological tests and functional scales were administered at 2 years follow up to all the patients. Results revealed that both at 1 and at 2 years follow up more patients in the aspecific group (18/19, 94% and 13/17, 76% respectively) than in the specific group (11/22, 50% and 5/15, 33% respectively) resulted to be cognitively impaired. Furthermore patients belonging to the specific group showed significantly less impaired tests compared with the aspecific group ones (p = 0.02) and a significant amelioration in the majority of the tests. On the contrary patients in the aspecific group did not change. The specific group subjects also perceived a subjective improvement in their cognitive performance, while the aspecific group patients did not. These results showed that short time domain specific cognitive rehabilitation is a useful treatment for patients with MS, shows very long lasting effects, compared to aspecific psychological interventions. Also subjective cognitive amelioration was found in patients submitted to domain specific treatment after 2 years. PMID:26941630

  15. The home stroke rehabilitation and monitoring system trial: a randomized controlled trial

    PubMed Central

    Linder, Susan M.; Rosenfeldt, Anson B.; Reiss, Aimee; Buchanan, Sharon; Sahu, Komal; Bay, Curtis R.; Wolf, Steven L.; Alberts, Jay L.

    2015-01-01

    Rationale Because many individuals post-stroke lack access to the quality and intensity of rehabilitation to improve upper extremity (UE) motor function, a home-based robotic-assisted UE rehabilitation device is being paired with an individualized home exercise program (HEP). Aims/Hypothesis The primary aim of this project is to determine the effectiveness of robotic-assisted home therapy compared to a home exercise program on UE motor recovery and health-related quality of life for stroke survivors in rural and underserved locations. The secondary aim is to explore whether initial degree of motor function of the upper limb may be a factor in predicting the extent to which patients with stroke may be responsive to a home therapy approach. The HEP intervention, when enhanced with robotic-assisted therapy will result in significantly better outcomes in motor function and quality of life. Design A total of 96 participants within six months of a single, unilateral ischemic or hemorrhagic stroke will be recruited in this prospective, single-blind, multi-site randomized clinical trial. Study Outcomes The primary outcome is the change in UE function using the Action Research Arm Test. Secondary outcomes include changes in: UE function (Wolf Motor Function Test), UE impairment (UE portion of the Fugl-Meyer Test), self-reported quality of life (Stroke Impact Scale), and affect (Centers for Epidemiologic Studies Depression Scale). Discussion Similar or greater improvements in UE function using the combined robotic-HEP intervention compared to HEP alone will be interpreted as evidence that supports the introduction of in-home technology to augment the recovery of function post-stroke. PMID:23280269

  16. Systematic review: The relation between nutrition and nosocomial pneumonia: randomized trials in critically ill patients

    PubMed Central

    1997-01-01

    Objective To review the effect of enteral nutrition on nosocomial pneumonia in critically ill patients as summarized in randomized clinical trials. Study identification and selection Studies were identified through MEDLINE, SCISEARCH, EMBASE, the Cochrane Library, bibliographies of primary and review articles, and personal files. Through duplicate independent review, we selected randomized trials evaluating approaches to nutrition and their relation to nosocomial pneumonia. Data abstraction In duplicate, independently, we abstracted key data on the design features, population, intervention and outcomes of the studies. Results We identified four trials of enteral vs total parenteral nutrition, one trial of early enteral nutrition vs delayed enteral nutrition, one trial of gastric vs jejunal tube feeding, one trial of intermittent vs continuous enteral feeding, and three trials evaluating different enteral feeding formulae. Sample sizes were small, pneumonia definitions were variable and blinded outcome assessment was infrequent. Randomized trial evidence is insufficient to draw conclusions about the relation between enteral nutrition and nosocomial pneumonia. Conclusions Nutritional interventions in critically ill patients appear to have a modest and inconsistent effect on nosocomial pneumonia. This body of evidence neither supports nor refutes the gastropulmonary route of infection. PMID:11094461

  17. Blinding Techniques in Randomized Controlled Trials of Laser Therapy: An Overview and Possible Solution

    PubMed Central

    Chow, Roberta; Pirotta, Marie

    2008-01-01

    Low-level laser therapy has evidence accumulating about its effectiveness in a variety of medical conditions. We reviewed 51 double blind randomized controlled trials (RCTs) of laser treatment. Analysis revealed 58% of trials showed benefit of laser over placebo. However, less than 5% of the trials had addressed beam disguise or allocation concealment in the laser machines used. Many of the trials used blinding methods that rely on staff cooperation and are therefore open to interference or bias. This indicates significant deficiencies in laser trial methodology. We report the development and preliminary testing of a novel laser machine that can blind both patient and operator to treatment allocation without staff participation. The new laser machine combines sealed preset and non-bypassable randomization codes, decoy lights and sound, and a conical perspex tip to overcome laser diode glow detection. PMID:18955233

  18. Beyond Randomized Controlled Trials in Attempted Suicide Research

    ERIC Educational Resources Information Center

    Hatcher, Simon; Sharon, Cynthia; Coggan, Carol

    2009-01-01

    There is a lack of evidence about what is the best treatment for people who present to hospital after self harm. Most treatment trials have been small and involved unrepresentative groups of patients which result in inconclusive findings. Here we note some of the characteristics of attempted suicide which make it a difficult subject to study. We…

  19. Exercise Training and Weight Gain in Obese Pregnant Women: A Randomized Controlled Trial (ETIP Trial)

    PubMed Central

    Garnæs, Kirsti Krohn; Mørkved, Siv; Salvesen, Øyvind; Moholdt, Trine

    2016-01-01

    of 0.1 (95% CI 0.02, 0.95; p = 0.04). Systolic blood pressure was significantly lower in the exercise group (mean 120.4 mm Hg) compared to the control group (mean 128.1 mm Hg), with a mean difference of −7.73 mm Hg (95% CI −13.23, −2.22; p = 0.006). No significant between-group differences were seen in diastolic blood pressure, blood measurements, skinfold thickness, or body composition in late pregnancy. In per protocol analyses, late pregnancy systolic blood pressure was 115.7 (95% CI 110.0, 121.5) mm Hg in the exercise group (significant between-group difference, p = 0.001), and diastolic blood pressure was 75.1 (95% CI 71.6, 78.7) mm Hg (significant between-group difference, p = 0.02). We had planned to recruit 150 women into the trial; hence, under-recruitment represents a major limitation of our results. Another limitation to our study was the low adherence to the exercise program, with only 50% of the women included in the intention-to-treat analysis adhering as described in the study protocol. Conclusions In this trial we did not observe a reduction in GWG among overweight/obese women who received a supervised exercise training program during their pregnancy. The incidence of GDM in late pregnancy seemed to be lower in the women randomized to exercise training than in the women receiving standard maternity care only. Systolic blood pressure in late pregnancy was also apparently lower in the exercise group than in the control group. These results indicate that supervised exercise training might be beneficial as a part of standard pregnancy care for overweight/obese women. Trial Registration ClinicalTrials.gov NCT01243554 PMID:27459375

  20. Acupuncture as a treatment for functional dyspepsia: design and methods of a randomized controlled trial

    PubMed Central

    Zheng, Hui; Tian, Xiao-ping; Li, Ying; Liang, Fan-rong; Yu, Shu-guang; Liu, Xu-guang; Tang, Yong; Yang, Xu-guang; Yan, Jie; Sun, Guo-jie; Chang, Xiao-rong; Zhang, Hong-xing; Ma, Ting-ting; Yu, Shu-yuan

    2009-01-01

    Background Acupuncture is widely used in China to treat functional dyspepsia (FD). However, its effectiveness in the treatment of FD, and whether FD-specific acupoints exist, are controversial. So this study aims to determine if acupuncture is an effective treatment for FD and if acupoint specificity exists according to traditional acupuncture meridians and acupoint theories. Design This multicenter randomized controlled trial will include four acupoint treatment groups, one non-acupoint control group and one drug (positive control) group. The four acupoint treatment groups will focus on: (1) specific acupoints of the stomach meridian; (2) non-specific acupoints of the stomach meridian; (3) specific acupoints of alarm and transport points; and (4) acupoints of the gallbladder meridian. These four groups of acupoints are thought to differ in terms of clinical efficacy, according to traditional acupuncture meridians and acupoint theories. A total of 120 FD patients will be included in each group. Each patient will receive 20 sessions of acupuncture treatment over 4 weeks. The trial will be conducted in eight hospitals located in three centers of China. The primary outcomes in this trial will include differences in Nepean Dyspepsia Index scores and differences in the Symptom Index of Dyspepsia before randomization, 2 weeks and 4 weeks after randomization, and 1 month and 3 months after completing treatment. Discussion The important features of this trial include the randomization procedures (controlled by a central randomization system), a standardized protocol of acupuncture manipulation, and the fact that this is the first multicenter randomized trial of FD and acupuncture to be performed in China. The results of this trial will determine whether acupuncture is an effective treatment for FD and whether using different acupoints or different meridians leads to differences in clinical efficacy. Trial registration number Clinical Trials.gov Identifier: NCT00599677

  1. Inadequate reporting of research ethics review and informed consent in cluster randomised trials: review of random sample of published trials

    PubMed Central

    McRae, Andrew D; Weijer, Charles; Bennett, Carol; Dixon, Stephanie; Taleban, Julia; Skea, Zoe; Eccles, Martin P; Brehaut, Jamie C; Donner, Allan; Saginur, Raphael; Boruch, Robert F; Grimshaw, Jeremy M

    2011-01-01

    Objectives To investigate the extent to which authors of cluster randomised trials adhered to two basic requirements of the World Medical Association’s Declaration of Helsinki and the International Committee of Medical Journal Editors’ uniform requirements for manuscripts (namely, reporting of research ethics review and informed consent), to determine whether the adequacy of reporting has improved over time, and to identify characteristics of cluster randomised trials associated with reporting of ethics practices. Design Review of a random sample of published cluster randomised trials from an electronic search in Medline. Setting Cluster randomised trials in health research published in English language journals from 2000 to 2008. Study sample 300 cluster randomised trials published in 150 journals. Results 77 (26%, 95% confidence interval 21% to 31%) trials failed to report ethics review. The proportion reporting ethics review increased significantly over time (P<0.001). Trials with data collection interventions at the individual level were more likely to report ethics review than were trials that used routine data sources only (79% (n=151) v 55% (23); P=0.008). Trials that accounted for clustering in the design and analysis were more likely to report ethics review. The median impact factor of the journal of publication was higher for trials that reported ethics review (3.4 v 2.3; P<0.001). 93 (31%, 26% to 36%) trials failed to report consent. Reporting of consent increased significantly over time (P<0.001). Trials with interventions targeting participants at the individual level were more likely to report consent than were trials with interventions targeting the cluster level (87% (90) v 48% (41); P<0.001). Trials with data collection interventions at the individual level were more likely to report consent than were those that used routine data sources only (78% (146) v 29% (11); P<0.001). Conclusions Reporting of research ethics protections in cluster

  2. An Adaptive Physical Activity Intervention for Overweight Adults: A Randomized Controlled Trial

    PubMed Central

    Adams, Marc A.; Sallis, James F.; Norman, Gregory J.; Hovell, Melbourne F.; Hekler, Eric B.; Perata, Elyse

    2013-01-01

    Background Physical activity (PA) interventions typically include components or doses that are static across participants. Adaptive interventions are dynamic; components or doses change in response to short-term variations in participant's performance. Emerging theory and technologies make adaptive goal setting and feedback interventions feasible. Objective To test an adaptive intervention for PA based on Operant and Behavior Economic principles and a percentile-based algorithm. The adaptive intervention was hypothesized to result in greater increases in steps per day than the static intervention. Methods Participants (N = 20) were randomized to one of two 6-month treatments: 1) static intervention (SI) or 2) adaptive intervention (AI). Inactive overweight adults (85% women, M = 36.9±9.2 years, 35% non-white) in both groups received a pedometer, email and text message communication, brief health information, and biweekly motivational prompts. The AI group received daily step goals that adjusted up and down based on the percentile-rank algorithm and micro-incentives for goal attainment. This algorithm adjusted goals based on a moving window; an approach that responded to each individual's performance and ensured goals were always challenging but within participants' abilities. The SI group received a static 10,000 steps/day goal with incentives linked to uploading the pedometer's data. Results A random-effects repeated-measures model accounted for 180 repeated measures and autocorrelation. After adjusting for covariates, the treatment phase showed greater steps/day relative to the baseline phase (p<.001) and a group by study phase interaction was observed (p = .017). The SI group increased by 1,598 steps/day on average between baseline and treatment while the AI group increased by 2,728 steps/day on average between baseline and treatment; a significant between-group difference of 1,130 steps/day (Cohen's d = .74). Conclusions The adaptive

  3. The role of exercise in modifying outcomes for people with multiple sclerosis: a randomized trial

    PubMed Central

    2013-01-01

    Background Despite the commonly known benefits of exercise and physical activity evidence shows that persons Multiple Sclerosis (MS) are relatively inactive yet physical activity may be even more important in a population facing functional deterioration. No exercise is effective if it is not done and people with MS face unique barriers to exercise engagement which need to be overcome. We have developed and pilot tested a Multiple Sclerosis Tailored Exercise Program (MSTEP) and it is ready to be tested against general guidelines for superiority and ultimately for its impact on MS relevant outcomes. The primary research question is to what extent does an MS Tailored Exercise Program (MSTEP) result in greater improvements in exercise capacity and related outcomes over a one year period in comparison to a program based on general guidelines for exercise among people with MS who are sedentary and wish to engage in exercise as part of MS self-management. Methods/Design The proposed study is an assessor-blind, parallel-group, randomized controlled trial (RCT). The duration of the intervention will be one year with follow-up to year two. The targeted outcomes are exercise capacity, functional ambulation, strength, and components of quality of life including frequency and intensity of fatigue symptoms, mood, global physical function, health perception, and objective measures of activity level. Logistic regression will be used to test the main hypothesis related to the superiority of the MSTEP program based on a greater proportion of people making a clinically relevant gain in exercise capacity at 1 year and at 2 years, using an intention-to-treat approach. Sample size will be 240 (120 per group). Discussion The MS community is clearly looking for interventions to help alleviate the disabling sequelae of MS and promote health. Exercise is a well-known intervention which has known benefits to all, yet few exercise regularly. For people with MS, the role of exercise in MS

  4. Reporting of Positive Results in Randomized Controlled Trials of Mindfulness-Based Mental Health Interventions

    PubMed Central

    Coronado-Montoya, Stephanie; Levis, Alexander W.; Kwakkenbos, Linda; Steele, Russell J.; Turner, Erick H.; Thombs, Brett D.

    2016-01-01

    Background A large proportion of mindfulness-based therapy trials report statistically significant results, even in the context of very low statistical power. The objective of the present study was to characterize the reporting of “positive” results in randomized controlled trials of mindfulness-based therapy. We also assessed mindfulness-based therapy trial registrations for indications of possible reporting bias and reviewed recent systematic reviews and meta-analyses to determine whether reporting biases were identified. Methods CINAHL, Cochrane CENTRAL, EMBASE, ISI, MEDLINE, PsycInfo, and SCOPUS databases were searched for randomized controlled trials of mindfulness-based therapy. The number of positive trials was described and compared to the number that might be expected if mindfulness-based therapy were similarly effective compared to individual therapy for depression. Trial registries were searched for mindfulness-based therapy registrations. CINAHL, Cochrane CENTRAL, EMBASE, ISI, MEDLINE, PsycInfo, and SCOPUS were also searched for mindfulness-based therapy systematic reviews and meta-analyses. Results 108 (87%) of 124 published trials reported ≥1 positive outcome in the abstract, and 109 (88%) concluded that mindfulness-based therapy was effective, 1.6 times greater than the expected number of positive trials based on effect size d = 0.55 (expected number positive trials = 65.7). Of 21 trial registrations, 13 (62%) remained unpublished 30 months post-trial completion. No trial registrations adequately specified a single primary outcome measure with time of assessment. None of 36 systematic reviews and meta-analyses concluded that effect estimates were overestimated due to reporting biases. Conclusions The proportion of mindfulness-based therapy trials with statistically significant results may overstate what would occur in practice. PMID:27058355

  5. Reporting quality of stepped wedge design randomized trials: a systematic review protocol

    PubMed Central

    Thabane, Alex; Dennis, Brittany B; Gajic-Veljanoski, Olga; Paul, James; Thabane, Lehana

    2016-01-01

    Background Stepped wedge design (SWD) is a cluster randomized controlled trial (RCT) design that sequentially rolls out intervention to all clusters at varying time points. Being a relatively new design method, reporting quality has yet to be explored, and this review will seek to fill this gap in knowledge. Objectives The objectives of this review are: 1) to assess the quality of SWD trial reports based on the CONSORT guidelines or CONSORT extension to cluster RCTs; 2) to assess the completeness of reporting of SWD trial abstracts using the CONSORT extension for abstracts; 3) to assess the reporting of sample size details in SWD trial reports or protocols; 4) to assess the completeness of reporting of SWD trial protocols according to SPIRIT guidelines; 5) to assess the consistency between the trial registration information and final SWD trial reports; and 6) to assess the consistency of what is reported in the abstracts and main text of the SWD trial reports. We will also explore factors that are associated with the completeness of reporting. Methods We will search MEDLINE, EMBASE, Web of Science, CINAHL, and PsycINFO for all randomized controlled trials utilizing SWD. Details from eligible papers will be extracted in duplicate. Demographic statistics obtained from the data extraction will be analyzed to answer the primary objectives pertaining to the reporting quality of several aspects of a published paper, as well as to explore possible temporal trends and consistency between abstracts, trial registration information, and final published articles. Discussion Findings from this review will establish the reporting quality of SWD trials and inform academics and clinicians on their completeness and consistency. Results of this review will influence future trials and improve the overall quality and reporting of SWD trials. PMID:27468249

  6. The CASCADE trial: effectiveness of ceramic versus PEEK cages for anterior cervical discectomy with interbody fusion; protocol of a blinded randomized controlled trial

    PubMed Central

    2013-01-01

    Background Anterior cervical discectomy with interbody fusion cages is considered the standard surgical procedure in patients with cervical disc herniation. However, PEEK or metal cages have some undesirable imaging characteristics, leading to a search for alternative materials not creating artifacts on images; silicon nitride ceramic. Whether patients treated with silicon nitride ceramic cages have similar functional outcome as patients treated with PEEK cages is not known. We present the design of the CASCADE trial on effectiveness of ceramic cages versus PEEK cages in patients with cervical disc herniation and/or osteophytes. Methods/Design Patients (age 18–75 years) with monoradicular symptoms in one or both arms lasting more than 8 weeks, due to disc herniation and/or osteophytes, are eligible for the trial. The study is designed as a randomized controlled equivalence trial in which patients are blinded to the type of cage for 1 year. The total follow-up period is 2 years. The primary outcome measure is improvement in the Neck and Disability Index (NDI). Secondary outcomes measures include improvement in arm pain and neck pain (VAS), SF-36 and patients' perceived recovery. The final elements of comparison are perioperative statistics including operating time, blood loss, length of hospital stay, and adverse events. Lateral plane films at each follow-up visit and CT scan (at 6 months) will be used to judge fusion and the incidence of subsidence. Based on a power of 90% and assuming 8% loss to follow-up, 100 patients will be randomized into the 2 groups. The first analysis will be conducted when all patients have 1 year of follow-up, and the groups will be followed for 1 additional year to judge stability of outcomes. Discussion While the new ceramic cage has received the CE Mark based on standard compliance and animal studies, a randomized comparative study with the golden standard product will provide more conclusive information for clinicians

  7. Phase IIB/III Trial of Tenecteplase in Acute Ischemic Stroke: Results of a Prematurely Terminated Randomized Clinical Trial

    PubMed Central

    Haley, E. Clarke; Thompson, John L.P.; Grotta, James C.; Lyden, Patrick D.; Hemmen, Thomas G.; Brown, Devin L.; Fanale, Christopher; Libman, Richard; Kwiatkowski, Thomas G.; Llinas, Rafael H.; Levine, Steven R.; Johnston, Karen C.; Buchsbaum, Richard; Levy, Gilberto; Levin, Bruce

    2010-01-01

    Background: Intravenous alteplase (rt-PA) remains the only approved treatment for acute ischemic stroke, but its use remains limited. In a previous pilot dose-escalation study, intravenous tenecteplase showed promise as a potentially safer alternative. Therefore, a Phase IIB clinical trial was begun to a) choose a best dose of tenecteplase to carry forward, and b) to provide evidence for either promise or futility of further testing of tenecteplase versus rt-PA. If promise was established, then the trial would continue as a Phase III efficacy trial comparing the selected tenecteplase dose to standard rt-PA. Methods: The trial began as a small, multi-center, randomized, double-blind, controlled clinical trial comparing 0.1, 0.25, and 0.4 mg/kg tenecteplase with standard 0.9 mg/kg rt-PA in patients with acute stroke within 3 hours of onset. An adaptive sequential design used an early (24 hour) assessment of major neurological improvement balanced against occurrence of symptomatic intracranial hemorrhage (ICH) to choose a “best” dose of tenecteplase to carry forward. Once a “best” dose was established, the trial was to continue until at least 100 pairs of the selected tenecteplase dose versus standard rt-PA could be compared by 3 month outcome using the modified Rankin Scale in an interim analysis. Decision rules were devised to yield a clear recommendation to either stop for futility or to continue into Phase III. Results: The trial was prematurely terminated for slow enrollment after only 112 patients had been randomized at 8 clinical centers between 2006 and 2008. The 0.4 mg/kg dose was discarded as inferior after only 73 patients were randomized, but the selection procedure was still unable to distinguish between 0.1 mg/kg and 0.25 mg/kg as a propitious dose at the time the trial was stopped. There were no statistically persuasive differences in 3 month outcomes between the remaining tenecteplase groups and rt-PA. Symptomatic ICH rates were highest in the

  8. Randomized controlled trials in frontotemporal dementia: cognitive and behavioral outcomes

    PubMed Central

    2014-01-01

    Progress has been made in understanding the genetics and molecular biology of frontotemporal dementia (FTD). Targets for intervention have been identified, therapies are being developed, and clinical trials are advancing. A major challenge for FTD research is that multiple underlying pathologies can be associated with heterogeneous phenotypes. The neuropsychological profiles associated with FTD spectrum disorders often include executive dysfunction, language impairments and behavioral disturbance. Behavioral variant FTD is characterized by an initial presentation of changes in personality, behavior and/or emotion, which are often difficult to objectively capture using traditional neuropsychological measures. The two principal language variants of FTD are Progressive Nonfluent Aphasia (PNFA) with predominant agrammatic/non-fluent impairments and Semantic Dementia (SD) with semantic impairments and visual agnosia. Selection of appropriate endpoints for clinical trials is critical to ensure that the measures are adequately sensitive to detect change, yet specific enough to isolate signal from noise, and acceptable to regulatory agencies. Given the anticipated potential for small effect sizes, measures must be able to identify small incremental changes over time. It is also imperative that the measures provide adequate coverage of the constructs or behaviors of interest. Selected outcome measures should be suitable for repeat administration, yet relatively robust to practice effects to ensure that observed changes reflect true signal variance and not residual effects due to repeated measurement or poor reliability. To facilitate widespread adoption as an endpoint, measures should be readily accessible. We provide several examples of potential global, composite, and individual cognitive measures, as well as behavioral measures promising for FTD trials. Development and application of appropriate trial outcomes is critically important to success in advancing new

  9. Randomized controlled trials in frontotemporal dementia: cognitive and behavioral outcomes.

    PubMed

    Miller, Justin B; Banks, Sarah J; Léger, Gabriel C; Cummings, Jeffrey L

    2014-01-01

    Progress has been made in understanding the genetics and molecular biology of frontotemporal dementia (FTD). Targets for intervention have been identified, therapies are being developed, and clinical trials are advancing. A major challenge for FTD research is that multiple underlying pathologies can be associated with heterogeneous phenotypes. The neuropsychological profiles associated with FTD spectrum disorders often include executive dysfunction, language impairments and behavioral disturbance. Behavioral variant FTD is characterized by an initial presentation of changes in personality, behavior and/or emotion, which are often difficult to objectively capture using traditional neuropsychological measures. The two principal language variants of FTD are Progressive Nonfluent Aphasia (PNFA) with predominant agrammatic/non-fluent impairments and Semantic Dementia (SD) with semantic impairments and visual agnosia. Selection of appropriate endpoints for clinical trials is critical to ensure that the measures are adequately sensitive to detect change, yet specific enough to isolate signal from noise, and acceptable to regulatory agencies. Given the anticipated potential for small effect sizes, measures must be able to identify small incremental changes over time. It is also imperative that the measures provide adequate coverage of the constructs or behaviors of interest. Selected outcome measures should be suitable for repeat administration, yet relatively robust to practice effects to ensure that observed changes reflect true signal variance and not residual effects due to repeated measurement or poor reliability. To facilitate widespread adoption as an endpoint, measures should be readily accessible. We provide several examples of potential global, composite, and individual cognitive measures, as well as behavioral measures promising for FTD trials. Development and application of appropriate trial outcomes is critically important to success in advancing new

  10. Resampling the N9741 Trial to Compare Tumor Dynamic Versus Conventional End Points in Randomized Phase II Trials

    PubMed Central

    Sharma, Manish R.; Gray, Elizabeth; Goldberg, Richard M.; Sargent, Daniel J.; Karrison, Theodore G.

    2015-01-01

    Purpose The optimal end point for randomized phase II trials of anticancer therapies remains controversial. We simulated phase II trials by resampling patients from N9741, a randomized phase III trial of chemotherapy regimens for metastatic colorectal cancer, and compared the power of various end points to detect the superior therapy (FOLFOX [infusional fluorouracil, leucovorin, and oxaliplatin] had longer overall survival than both IROX [irinotecan plus oxaliplatin] and IFL [irinotecan and bolus fluorouracil plus leucovorin]). Methods Tumor measurements and progression-free survival (PFS) data were obtained for 1,471 patients; 1,002 had consistently measured tumors and were resampled (5,000 replicates) to simulate two-arm, randomized phase II trials with α = 0.10 (one sided) and 20 to 80 patients per arm. End points included log ratio of tumor size at 6, 12, and 18 weeks relative to baseline; time to tumor growth (TTG), estimated using a nonlinear mixed-effects model; and PFS. Arms were compared using rank sum tests for log ratio and TTG and a log-rank test for PFS. Results For FOLFOX versus IFL, TTG and PFS had similar power, with both exceeding the power of log ratio at 18 weeks; for FOLFOX versus IROX, TTG and log ratio at 18 weeks had similar power, with both exceeding the power of PFS. The best end points exhibited > 80% power with 60 to 80 patients per arm. Conclusion TTG is a powerful end point for randomized phase II trials of cytotoxic therapies in metastatic colorectal cancer; it was either comparable or superior to PFS and log ratio at 18 weeks. Additional studies will be needed to clarify the potential of TTG as a phase II end point. PMID:25349295

  11. Influence of Obesity on Breast Density Reduction by Omega-3 Fatty Acids: Evidence from a Randomized Clinical Trial.

    PubMed

    Sandhu, Narinder; Schetter, Susann E; Liao, Jason; Hartman, Terryl J; Richie, John P; McGinley, John; Thompson, Henry J; Prokopczyk, Bogdan; DuBrock, Cynthia; Signori, Carina; Hamilton, Christopher; Calcagnotto, Ana; Trushin, Neil; Aliaga, Cesar; Demers, Laurence M; El-Bayoumy, Karam; Manni, Andrea

    2016-04-01

    Preclinical data indicate that omega-3 fatty acids (n-3FA) potentiate the chemopreventive effect of the antiestrogen (AE) tamoxifen against mammary carcinogenesis. The role of n-3FA in breast cancer prevention in humans is controversial. Preclinical and epidemiologic data suggest that n-3FA may be preferentially protective in obese subjects. To directly test the protective effect of n-3FA against breast cancer, we conducted a 2-year, open-label randomized clinical trial in 266 healthy postmenopausal women (50% normal weight, 30% overweight, 20% obese) with high breast density (BD; ≥25%) detected on their routine screening mammograms. Eligible women were randomized to one of the following five groups (i) no treatment, control; (ii) raloxifene 60 mg; (iii) raloxifene 30 mg; (iv) n-3FA lovaza 4 g; and (v) lovaza 4 g plus raloxifene 30 mg. The 2-year change in BD, a validated biomarker of breast cancer risk, was the primary endpoint of the study. In subset analysis, we tested the prespecified hypothesis that body mass index (BMI) influences the relationship between plasma n-3FA on BD. While none of the interventions affected BD in the intention-to-treat analysis, increase in plasma DHA was associated with a decrease in absolute breast density but only in participants with BMI >29. Our results suggest that obese women may preferentially experience breast cancer risk reduction from n-3FA administration. PMID:26714774

  12. Complementary/alternative therapies for premenstrual syndrome: a systematic review of randomized controlled trials.

    PubMed

    Stevinson, C; Ernst, E

    2001-07-01

    Complementary/alternative therapies are popular with women who have premenstrual syndrome. This systematic review was designed to determine whether use of such therapies is supported by evidence of effectiveness from rigorous clinical trials. Trials were located through searching 7 databases and checking the reference lists of articles. Randomized controlled trials investigating a complementary/alternative therapy in women with premenstrual syndrome published in the peer-reviewed literature were included in the review. Twenty-seven trials were included investigating herbal medicine (7 trials), homeopathy (1), dietary supplements (13), relaxation (1), massage (1), reflexology (1) chiropractic (1), and biofeedback (2). Despite some positive findings, the evidence was not compelling for any of these therapies, with most trials suffering from various methodological limitations. On the basis of current evidence, no complementary/alternative therapy can be recommended as a treatment for premenstrual syndrome. PMID:11483933

  13. A Randomized Violence Prevention Trial with Comparison: Responses by Gender

    ERIC Educational Resources Information Center

    Griffin, James P., Jr.; Chen, Dungtsa; Eubanks, Adriane; Brantley, Katrina M.; Willis, Leigh A.

    2007-01-01

    Using random assignment of students to two intervention groups and a comparison school sample, the researchers evaluated a three-group school-based violence prevention program. The three groups were (1) a whole-school intervention, (2) whole-school, cognitive-behavioral and cultural enrichment training, and (3) no violence prevention. The…

  14. Randomized Trial of Suicide Gatekeeper Training for Social Work Students

    ERIC Educational Resources Information Center

    Jacobson, Jodi M.; Osteen, Phillip J.; Sharpe, Tanya L.; Pastoor, Jennifer B.

    2012-01-01

    Problem: Education and research on social work's role in preventing client suicide is limited. Method: Seventy advanced master of social work students were randomly assigned to either the training group (Question, Persuade, and Referral suicide gatekeeper training) or the control group. Outcomes measured over time included suicide knowledge,…

  15. Attitudes Toward Participation in Breast Cancer Randomized Clinical Trials in the African American Community

    PubMed Central

    Linden, Hannah M.; Reisch, Lisa M.; Hart, Alton; Harrington, Margaret A.; Nakano, Connie; Jackson, J. Carey; Elmore, Joann G.

    2013-01-01

    Participation of African Americans in research trials is low. Understanding the perspectives of African American patients toward participation in clinical trials is essential to understanding the disparities in participation rates compared with whites. A qualitative study was conducted to discover attitudes of the African American community regarding willingness to participate in breast cancer screening and randomized clinical trials. Six focus groups consisting of 8 to 11 African American women (N = 58), aged 30 to 65, were recruited from local churches. Focus group sessions involved a 2-hour audiotaped discussion facilitated by 2 moderators. A breast cancer randomized clinical trial involving an experimental breast cancer treatment was discussed to identify the issues related to willingness to participate in such research studies. Six themes surrounding willingness to participate in randomized clinical trials were identified: (1) Significance of the research topic to the individual and/or community; (2) level of trust in the system; (3) understanding of the elements of the trial; (4) preference for “natural treatments” or “religious intervention” over medical care; (5) cost-benefit analysis of incentives and barriers; and (6) openness to risk versus a preference for proven treatments. The majority (80%) expressed willingness or open-mindedness to the idea of participating in the hypothetical trial. Lessons learned from this study support the selection of a culturally diverse research staff and can guide the development of research protocols, recruitment efforts, and clinical procedures that are culturally sensitive and relevant. PMID:17666974

  16. Reporting of noninferiority and equivalence randomized trials: extension of the CONSORT 2010 statement.

    PubMed

    Piaggio, Gilda; Elbourne, Diana R; Pocock, Stuart J; Evans, Stephen J W; Altman, Douglas G

    2012-12-26

    The CONSORT (Consolidated Standards of Reporting Trials) Statement, which includes a checklist and a flow diagram, is a guideline developed to help authors improve the reporting of the findings from randomized controlled trials. It was updated most recently in 2010. Its primary focus is on individually randomized trials with 2 parallel groups that assess the possible superiority of one treatment compared with another. The CONSORT Statement has been extended to other trial designs such as cluster randomization, and recommendations for noninferiority and equivalence trials were made in 2006. In this article, we present an updated extension of the CONSORT checklist for reporting noninferiority and equivalence trials, based on the 2010 version of the CONSORT Statement and the 2008 CONSORT Statement for the reporting of abstracts, and provide illustrative examples and explanations for those items that differ from the main 2010 CONSORT checklist. The intent is to improve reporting of noninferiority and equivalence trials, enabling readers to assess the reliability of their results and conclusions. PMID:23268518

  17. Pancreatitis of biliary origin, optimal timing of cholecystectomy (PONCHO trial): study protocol for a randomized controlled trial

    PubMed Central

    2012-01-01

    Background After an initial attack of biliary pancreatitis, cholecystectomy minimizes the risk of recurrent biliary pancreatitis and other gallstone-related complications. Guidelines advocate performing cholecystectomy within 2 to 4 weeks after discharge for mild biliary pancreatitis. During this waiting period, the patient is at risk of recurrent biliary events. In current clinical practice, surgeons usually postpone cholecystectomy for 6 weeks due to a perceived risk of a more difficult dissection in the early days following pancreatitis and for logistical reasons. We hypothesize that early laparoscopic cholecystectomy minimizes the risk of recurrent biliary pancreatitis or other complications of gallstone disease in patients with mild biliary pancreatitis without increasing the difficulty of dissection and the surgical complication rate compared with interval laparoscopic cholecystectomy. Methods/Design PONCHO is a randomized controlled, parallel-group, assessor-blinded, superiority multicenter trial. Patients are randomly allocated to undergo early laparoscopic cholecystectomy, within 72 hours after randomization, or interval laparoscopic cholecystectomy, 25 to 30 days after randomization. During a 30-month period, 266 patients will be enrolled from 18 hospitals of the Dutch Pancreatitis Study Group. The primary endpoint is a composite endpoint of mortality and acute re-admissions for biliary events (that is, recurrent biliary pancreatitis, acute cholecystitis, symptomatic/obstructive choledocholithiasis requiring endoscopic retrograde cholangiopancreaticography including cholangitis (with/without endoscopic sphincterotomy), and uncomplicated biliary colics) occurring within 6 months following randomization. Secondary endpoints include the individual endpoints of the composite endpoint, surgical and other complications, technical difficulty of cholecystectomy and costs. Discussion The PONCHO trial is designed to show that early laparoscopic cholecystectomy

  18. How large are the nonspecific effects of acupuncture? A meta-analysis of randomized controlled trials

    PubMed Central

    2010-01-01

    Background While several recent large randomized trials found clinically relevant effects of acupuncture over no treatment or routine care, blinded trials comparing acupuncture to sham interventions often reported only minor or no differences. This raises the question whether (sham) acupuncture is associated with particularly potent nonspecific effects. We aimed to investigate the size of nonspecific effects associated with acupuncture interventions. Methods MEDLINE, Embase, Cochrane Central Register of Controlled Clinical Trials and reference lists were searched up to April 2010 to identify randomized trials of acupuncture for any condition, including both sham and no acupuncture control groups. Data were extracted by one reviewer and verified by a second. Pooled standardized mean differences were calculated using a random effects model with the inverse variance method. Results Thirty-seven trials with a total of 5754 patients met the inclusion criteria. The included studies varied strongly regarding patients, interventions, outcome measures, methodological quality and effect sizes reported. Among the 32 trials reporting a continuous outcome measure, the random effects standardized mean difference between sham acupuncture and no acupuncture groups was -0.45 (95% confidence interval, -0.57, -0.34; I2 = 54%; Egger's test for funnel plot asymmetry, P = 0.25). Trials with larger effects of sham over no acupuncture reported smaller effects of acupuncture over sham intervention than trials with smaller nonspecific effects (β = -0.39, P = 0.029). Conclusions Sham acupuncture interventions are often associated with moderately large nonspecific effects which could make it difficult to detect small additional specific effects. Compared to inert placebo interventions, effects associated with sham acupuncture might be larger, which would have considerable implications for the design and interpretation of clinical trials. PMID:21092261

  19. 78 FR 63479 - Meta-Analyses of Randomized Controlled Clinical Trials (RCTs) for the Evaluation of Risk To...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-24

    ... HUMAN SERVICES Food and Drug Administration Meta-Analyses of Randomized Controlled Clinical Trials (RCTs... scientific approaches for the conduct and assessment of meta-analyses of randomized controlled clinical... others from the general public, about the use of meta-analyses of randomized trials as a tool for...

  20. Protocol for the Osteoporosis Choice trial. A pilot randomized trial of a decision aid in primary care practice

    PubMed Central

    2009-01-01

    Background Bisphosphonates can reduce fracture risk in patients with osteoporosis, but many at-risk patients do not start or adhere to these medications. The aims of this study are to: (1) preliminarily evaluate the effect of an individualized 10-year osteoporotic fracture risk calculator and decision aid (OSTEOPOROSIS CHOICE) for postmenopausal women at risk for osteoporotic fractures; and (2) assess the feasibility and validity (i.e., absence of contamination) of patient-level randomization (vs. cluster randomization) in pilot trials of decision aid efficacy. Methods/Design This is a protocol for a parallel, 2-arm, randomized trial to compare an intervention group receiving OSTEOPOROSIS CHOICE to a control group receiving usual primary care. Postmenopausal women with bone mineral density T-scores of <-1.0, not receiving bisphosphonate therapy, and receiving care at participating primary care practices in and around Rochester, Minnesota, USA will be eligible to participate in the trial. We will measure the effect of OSTEOPOROSIS CHOICE on five outcomes: (a) patient knowledge regarding osteoporosis risk factors and treatment; (b) quality of the decision-making process for both the patient and clinician; (c) patient and clinician acceptability and satisfaction with the decision aid; (d) rate of bisphosphonate use and adherence, and (e) trial processes (e.g., ability to recruit participants, collect patient outcomes). To capture these outcomes, we will use patient and clinician surveys following each visit and video recordings of the clinical encounters. These video recordings will also allow us to determine the extent to which clinicians previously exposed to the decision aid were able to recreate elements of the decision aid with control patients (i.e., contamination). Pharmacy prescription profiles and follow-up phone interviews will assess medication start and adherence at 6 months. Discussion This pilot trial will provide evidence of feasibility, validity of

  1. CONSORT for Reporting Randomized Controlled Trials in Journal and Conference Abstracts: Explanation and Elaboration

    PubMed Central

    Hopewell, Sally; Clarke, Mike; Moher, David; Wager, Elizabeth; Middleton, Philippa; Altman, Douglas G; Schulz, Kenneth F

    2008-01-01

    Background Clear, transparent, and sufficiently detailed abstracts of conferences and journal articles related to randomized controlled trials (RCTs) are important, because readers often base their assessment of a trial solely on information in the abstract. Here, we extend the CONSORT (Consolidated Standards of Reporting Trials) Statement to develop a minimum list of essential items, which authors should consider when reporting the results of a RCT in any journal or conference abstract. Methods and Findings We generated a list of items from existing quality assessment tools and empirical evidence. A three-round, modified-Delphi process was used to select items. In all, 109 participants were invited to participate in an electronic survey; the response rate was 61%. Survey results were presented at a meeting of the CONSORT Group in Montebello, Canada, January 2007, involving 26 participants, including clinical trialists, statisticians, epidemiologists, and biomedical editors. Checklist items were discussed for eligibility into the final checklist. The checklist was then revised to ensure that it reflected discussions held during and subsequent to the meeting. CONSORT for Abstracts recommends that abstracts relating to RCTs have a structured format. Items should include details of trial objectives; trial design (e.g., method of allocation, blinding/masking); trial participants (i.e., description, numbers randomized, and number analyzed); interventions intended for each randomized group and their impact on primary efficacy outcomes and harms; trial conclusions; trial registration name and number; and source of funding. We recommend the checklist be used in conjunction with this explanatory document, which includes examples of good reporting, rationale, and evidence, when available, for the inclusion of each item. Conclusions CONSORT for Abstracts aims to improve reporting of abstracts of RCTs published in journal articles and conference proceedings. It will help

  2. Healthy Families New York (HFNY) Randomized Trial: Effects on Early Child Abuse and Neglect

    ERIC Educational Resources Information Center

    DuMont, Kimberly; Mitchell-Herzfeld, Susan; Greene, Rose; Lee, Eunju; Lowenfels, Ann; Rodriguez, Monica; Dorabawila, Vajeera

    2008-01-01

    Objective: To evaluate the effects of a home visiting program modeled after Healthy Families America on parenting behaviors in the first 2 years of life. Methods: A sample of 1173 families at risk for child abuse and neglect who met the criteria for Healthy Families New York (HFNY) was randomly assigned to either an intervention group that was…

  3. Effects of Aerobic Exercise on Overweight Children's Cognitive Functioning: A Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Davis, Catherine L.; Tomporowski, Phillip D.; Boyle, Colleen A.; Waller, Jennifer L.; Miller, Patricia H.; Naglieri, Jack A.; Gregoski, Mathew

    2007-01-01

    The study tested the effect of aerobic exercise training on executive function in overweight children. Ninety-four sedentary, overweight but otherwise healthy children (mean age = 9.2 years, body mass index [greater than or equal to] 85th percentile) were randomized to a low-dose (20 min/day exercise), high-dose (40 min/day exercise), or control…

  4. Efficacy of Yoga for Vasomotor Symptoms: A Randomized Controlled Trial

    PubMed Central

    Newton, Katherine M.; Reed, Susan D.; Guthrie, Katherine A.; Sherman, Karen J.; Booth-LaForce, Cathryn; Caan, Bette; Sternfeld, Barbara; Carpenter, Janet S.; Learman, Lee A.; Freeman, Ellen W.; Cohen, Lee S.; Joffe, Hadine; Anderson, Garnet L.; Larson, Joseph C.; Hunt, Julie R.; Ensrud, Kristine E.; LaCroix, Andrea Z.

    2013-01-01

    Objective To determine the efficacy of yoga in alleviating VMS frequency and bother. Methods Three by two factorial design, randomized, controlled. Eligible women were randomized to yoga (n=107), exercise (n=106), or usual activity (n=142), and were simultaneously randomized to double-blind comparison of omega-3 fatty acid (n=177) or placebo (n=178) capsules. Yoga intervention was twelve, weekly, 90-minute yoga classes with daily home practice. Primary outcomes were VMS frequency and bother assessed by daily diaries at baseline, 6, and 12 weeks. Secondary outcomes included insomnia symptoms (Insomnia Severity Index) at baseline and 12 weeks. Results Among 249 randomized women, 237 (95%) completed 12-week assessments. Mean baseline VMS frequency was 7.4/day (95% CI 6.6, 8.1) in the yoga group and 8.0/day (95% CI 7.3, 8.7) in the usual activity group. Intent-to-treat analyses included all participants with response data (n=237). There was no difference between intervention groups in change in VMS frequency from baseline to 6 and 12 weeks (mean difference (yoga – usual activity) from baseline −0.3 (95% CI −1.1, 0.5) at 6 weeks and −0.3 (95% CI −1.2, 0.6) at 12 weeks (p=0.119 across both time points). Results were similar for VMS bother. At week 12, yoga was associated with an improvement in insomnia symptoms (mean difference [yoga-usual activity] in change –Insomnia Severity Index, 1.3 [95% CI −2.5, −0.1][p=0.007]). Conclusion Among healthy women, 12 weeks of yoga class plus home practice compared with usual activity did not improve VMS frequency or bother, but reduced insomnia symptoms. PMID:24045673

  5. Interpreting a randomized trial report: evidence-based practice for the clinician.

    PubMed

    Vidaeff, Alex C; Saade, George R; Belfort, Michael A

    2016-01-01

    The purpose of this article is to present a structured approach to help the reader with the objective interpretation of published randomized clinical trials. This process will promote an organized and critical appraisal of scientific evidence, which we believe to be an essential step prior to the introduction of published scientific findings into clinical practice. The reason to personally scrutinize and critically assess published reports is that the process of peer review is by no means perfect and methodological flaws can be uncovered, even in articles published in prestigious journals. The article elaborates on the substance of the consolidated standards of reporting trials (CONSORT) statements intended to facilitate the complete reporting of trials and aid in their critical assessment. The structure of the CONSORT guidelines was used as a basis for specific commentary, including cautions for the clinical interpretation, implications and impact of published randomized trial reports. PMID:26482527

  6. Key analytic considerations in design and analysis of randomized controlled trials in osteoarthritis

    PubMed Central

    Losina, Elena; Ranstam, Jonas; Collins, Jamie; Schnitzer, Thomas J; Katz, Jeffrey N.

    2016-01-01

    Objective To highlight methodologic challenges pertinent to design, analysis, and reporting of results of randomized clinical trials in OA and offer practical suggestions to overcome these challenges. Design The topics covered in this paper include subject selection, randomization, approaches to handling missing data, subgroup analysis, sample size, and issues related to changing design mid-way through the study. Special attention is given to standardizing the reporting of results and economic analyses. Results Key findings include the importance of blinding and concealment, the distinction between superiority and non-inferiority trials, the need to minimize missing data, and appropriate analysis and interpretation of subgroup effects. Conclusion Investigators may use the findings and recommendations advanced in this paper to guide design and conduct of randomized controlled trials of interventions for osteoarthritis. PMID:25952341

  7. Inference for the median residual life function in sequential multiple assignment randomized trials

    PubMed Central

    Kidwell, Kelley M.; Ko, Jin H.; Wahed, Abdus S.

    2014-01-01

    In survival analysis, median residual lifetime is often used as a summary measure to assess treatment effectiveness; it is not clear, however, how such a quantity could be estimated for a given dynamic treatment regimen using data from sequential randomized clinical trials. We propose a method to estimate a dynamic treatment regimen-specific median residual life (MERL) function from sequential multiple assignment randomized trials. We present the MERL estimator, which is based on inverse probability weighting, as well as, two variance estimates for the MERL estimator. One variance estimate follows from Lunceford, Davidian and Tsiatis’ 2002 survival function-based variance estimate and the other uses the sandwich estimator. The MERL estimator is evaluated, and its two variance estimates are compared through simulation studies, showing that the estimator and both variance estimates produce approximately unbiased results in large samples. To demonstrate our methods, the estimator has been applied to data from a sequentially randomized leukemia clinical trial. PMID:24254496

  8. The Method of Randomization for Cluster-Randomized Trials: Challenges of Including Patients with Multiple Chronic Conditions

    PubMed Central

    Esserman, Denise; Allore, Heather G.; Travison, Thomas G.

    2016-01-01

    Cluster-randomized clinical trials (CRT) are trials in which the unit of randomization is not a participant but a group (e.g. healthcare systems or community centers). They are suitable when the intervention applies naturally to the cluster (e.g. healthcare policy); when lack of independence among participants may occur (e.g. nursing home hygiene); or when it is most ethical to apply an intervention to all within a group (e.g. school-level immunization). Because participants in the same cluster receive the same intervention, CRT may approximate clinical practice, and may produce generalizable findings. However, when not properly designed or interpreted, CRT may induce biased results. CRT designs have features that add complexity to statistical estimation and inference. Chief among these is the cluster-level correlation in response measurements induced by the randomization. A critical consideration is the experimental unit of inference; often it is desirable to consider intervention effects at the level of the individual rather than the cluster. Finally, given that the number of clusters available may be limited, simple forms of randomization may not achieve balance between intervention and control arms at either the cluster- or participant-level. In non-clustered clinical trials, balance of key factors may be easier to achieve because the sample can be homogenous by exclusion of participants with multiple chronic conditions (MCC). CRTs, which are often pragmatic, may eschew such restrictions. Failure to account for imbalance may induce bias and reducing validity. This article focuses on the complexities of randomization in the design of CRTs, such as the inclusion of patients with MCC, and imbalances in covariate factors across clusters.

  9. Methods for testing theory and evaluating impact in randomized field trials

    PubMed Central

    Brown, C. Hendricks; Wang, Wei; Kellam, Sheppard G.; Muthén, Bengt O.; Petras, Hanno; Toyinbo, Peter; Poduska, Jeanne; Ialongo, Nicholas; Wyman, Peter A.; Chamberlain, Patricia; Sloboda, Zili; MacKinnon, David P.; Windham, Amy

    2008-01-01

    Randomized field trials provide unique opportunities to examine the effectiveness of an intervention in real world settings and to test and extend both theory of etiology and theory of intervention. These trials are designed not only to test for overall intervention impact but also to examine how impact varies as a function of individual level characteristics, context, and across time. Examination of such variation in impact requires analytical methods that take into account the trial’s multiple nested structure and the evolving changes in outcomes over time. The models that we describe here merge multilevel modeling with growth modeling, allowing for variation in impact to be represented through discrete mixtures—growth mixture models—and nonparametric smooth functions—generalized additive mixed models. These methods are part of an emerging class of multilevel growth mixture models, and we illustrate these with models that examine overall impact and variation in impact. In this paper, we define intent-to-treat analyses in group-randomized multilevel field trials and discuss appropriate ways to identify, examine, and test for variation in impact without inflating the Type I error rate. We describe how to make causal inferences more robust to misspecification of covariates in such analyses and how to summarize and present these interactive intervention effects clearly. Practical strategies for reducing model complexity, checking model fit, and handling missing data are discussed using six randomized field trials to show how these methods may be used across trials randomized at different levels. PMID:18215473

  10. Using Minitel Network and New Software Engineering Techniques for Randomized Clinical Trials Management

    PubMed Central

    Lepage, E.; Tavernier, H.; Bouhaddou, O.; Jais, JP.; Gisselbrecht, C.; Aurengo, A.; Boiron, M.

    1989-01-01

    The usual Randomized Clinical Trials (RCT) management using an anachronic procedure involving a flowsheet exchange between the remote centers and the coordinating center presents a number of inadequacies. Eligibility criteria are not always verified by the coordinating center before inclusion in the trial and randomization. Laboratory tests and therapeutic adjustments are frequently decided from memory by the clinician which often leads to data oversight and variability of therapeutic decisions. This results in protocol deviations and alteration of the efficiency of the RCT. HICREN is a medical consultation system designed to take into account the different difficulties encountered during RCT driving. The system integrates a clinical database with artificial intelligence technics to manage clinical trial data on non-expensive and widely available Minitel® terminals. Randomization is then possible, after eligibility criteria are satisfied, anytime and anywhere in France through the national telematic network. HICREN also includes an intuitive graphic interface to increase physician's compliance: a user friendly dialogue manager supports on line data entry with multi-windowing facilities and pull down menus. Interactive data validation is achieved through an interface to dedicated C programs. Patient follow up is achieved by an expert system that proposes appropriate dose of treatment according to the rules defined in the trial. At present, HICREN is implemented on the CISARC system for conducting three randomized clinical trials and one epidemiologic study.

  11. Application of dietary fiber in clinical enteral nutrition: A meta-analysis of randomized controlled trials

    PubMed Central

    Yang, Gang; Wu, Xiao-Ting; Zhou, Yong; Wang, Ying-Li

    2005-01-01

    AIM: To evaluate the effects of dietary fiber (DF) as a part of enteral nutrition (EN) formula on diarrhea, infection, and length of hospital stay. METHODS: Following electronic databases were searched for randomized controlled trials about DF: Chinese Biomedicine Database (CBM), MEDLINE, EMBASE and Cochrane Controlled Trials Register. RevMan 4.1 was used for statistical analysis. RESULTS: Seven randomized controlled trials with 400 pat-ients were included. The supplement of DF in EN was compared with standard enteral formula in five trials. Combined analysis did not show a significant reduction in occurrence of diarrhea, but there were valuable results for non-critically ill patients. Combined analysis of two trials observing the infection also did not show any valid evidence that DF could decrease the infection rate, though the length of hospital stay was reduced significantly. CONCLUSION: Based on the current eligible randomized controlled trials, there is no evidence that the value of DF in the diarrhea can be proved. Though length of hospital stay was shortened by the use of DF, there is no available evidence in preventing infection by DF. Further studies are needed for evaluating the value of DF in EN. PMID:15991297

  12. Acute migraine therapy: recent evidence from randomized comparative trials.

    PubMed

    Mett, Anna; Tfelt-Hansen, Peer

    2008-06-01

    (1) A wide array of data regarding acute migraine treatment are available, but few trials strictly adhere to International Headache Society guidelines for patient inclusion criteria.(2) Triptans appear to have similar efficacy profiles, but among newer triptans, almotriptan offers improved tolerability over sumatriptan.(3) Combination indomethacin/caffeine/prochlorperazine most likely has similar therapeutic efficacy to triptan therapy, with further research needed to complete understanding of any potential differences between these treatments.(4) Multi-targeted combination therapy with a triptan plus a non-steroidal anti-inflammatory (NSAID), such as sumatriptan/naproxen sodium, is more effective in acute migraine treatment than monotherapy with either agent alone.(5) It is unclear whether triptans offer clinically relevant benefits over aspirin or NSAIDs in migraine patients. Thus NSAIDs, particularly effervescent aspirin, should be considered the first-line treatment of migraine attacks. PMID:18451718

  13. Creation and implementation of a historical controls database from randomized clinical trials

    PubMed Central

    Desai, Jigar R; Bowen, Edward A; Danielson, Mark M; Allam, Rajasekhar R; Cantor, Michael N

    2013-01-01

    Background Ethical concerns about randomly assigning patients to suboptimal or placebo arms and the paucity of willing participants for randomization into control and experimental groups have renewed focus on the use of historical controls in clinical trials. Although databases of historical controls have been advocated, no published reports have described the technical and informatics issues involved in their creation. Objective To create a historical controls database by leveraging internal clinical trial data at Pfizer, focusing on patients who received only placebo in randomized controlled trials. Methods We transformed disparate clinical data sources by indexing, developing, and integrating clinical data within internal databases and archives. We focused primarily on trials mapped into a consistent standard and trials in the pain therapeutic area as a pilot. Results Of the more than 20 000 internal Pfizer clinical trials, 2404 completed placebo controlled studies with a parallel design were identified. Due to challenges with informed consent and data standards used in older clinical trials, studies completed before 2000 were excluded, yielding 1134 studies from which placebo subjects and associated clinical data were extracted. Conclusions It is technically feasible to pool portions of placebo populations through a stratification and segmentation approach for a historical placebo group database. A sufficiently large placebo controls database would enable previous distribution calculations on representative populations to supplement, not eliminate, the placebo arm of future clinical trials. Creation of an industry-wide placebo controls database, utilizing a universal standard, beyond the borders of Pfizer would add significant efficiencies to the clinical trial and drug development process. PMID:23449762

  14. Hypofractionated radiotherapy versus conventionally fractionated radiotherapy for patients with intermediate-risk localised prostate cancer: 2-year patient-reported outcomes of the randomised, non-inferiority, phase 3 CHHiP trial

    PubMed Central

    Wilkins, Anna; Mossop, Helen; Syndikus, Isabel; Khoo, Vincent; Bloomfield, David; Parker, Chris; Logue, John; Scrase, Christopher; Patterson, Helen; Birtle, Alison; Staffurth, John; Malik, Zafar; Panades, Miguel; Eswar, Chinnamani; Graham, John; Russell, Martin; Kirkbride, Peter; O'Sullivan, Joe M; Gao, Annie; Cruickshank, Clare; Griffin, Clare; Dearnaley, David; Hall, Emma

    2015-01-01

    , number ISRCTN97182923. Findings 2100 participants in the CHHiP trial consented to be included in the QoL substudy: 696 assigned to the 74 Gy schedule, 698 assigned to the 60 Gy schedule, and 706 assigned to the 57 Gy schedule. Of these individuals, 1659 (79%) provided data pre-radiotherapy and 1444 (69%) provided data at 24 months after radiotherapy. Median follow-up was 50·0 months (IQR 38·4–64·2) on April 9, 2014, which was the most recent follow-up measurement of all data collected before the QoL data were analysed in September, 2014. Comparison of 74 Gy in 37 fractions, 60 Gy in 20 fractions, and 57 Gy in 19 fractions groups at 2 years showed no overall bowel bother in 269 (66%), 266 (65%), and 282 (65%) men; very small bother in 92 (22%), 91 (22%), and 93 (21%) men; small bother in 26 (6%), 28 (7%), and 38 (9%) men; moderate bother in 19 (5%), 23 (6%), and 21 (5%) men, and severe bother in four (<1%), three (<1%) and three (<1%) men respectively (74 Gy vs 60 Gy, ptrend=0.64, 74 Gy vs 57 Gy, ptrend=0·59). We saw no differences between treatment groups in change of bowel bother score from baseline or pre-radiotherapy to 24 months. Interpretation The incidence of patient-reported bowel symptoms was low and similar between patients in the 74 Gy control group and the hypofractionated groups up to 24 months after radiotherapy. If efficacy outcomes from CHHiP show non-inferiority for hypofractionated treatments, these findings will add to the growing evidence for moderately hypofractionated radiotherapy schedules becoming the standard treatment for localised prostate cancer. Funding Cancer Research UK, Department of Health, and the National Institute for Health Research Cancer Research Network. PMID:26522334

  15. Saffron (Crocus sativus L.) and major depressive disorder: a meta-analysis of randomized clinical trials

    PubMed Central

    Hausenblas, Heather Ann; Saha, Debbie; Dubyak, Pamela Jean; Anton, Stephen Douglas

    2015-01-01

    BACKGROUND Due to safety concerns and side effects of many antidepressant medications, herbal psychopharmacology research has increased, and herbal remedies are becoming increasingly popular as alternatives to prescribed medications for the treatment of major depressive disorder (MDD). Of these, accumulating trials reveal positive effects of the spice saffron (Crocus sativus L.) for the treatment of depression. A comprehensive and statistical review of the clinical trials examining the effects of saffron for treatment of MDD is warranted. OBJECTIVE The purpose of this study was to conduct a meta-analysis of published randomized controlled trials examining the effects of saffron supplementation on symptoms of depression among participants with MDD. SEARCH STRATEGY We conducted electronic and non-electronic searches to identify all relevant randomized, double-blind controlled trials. Reference lists of all retrieved articles were searched for relevant studies. INCLUSION CRITERIA The criteria for study selection included the following: (1) adults (aged 18 and older) with symptoms of depression, (2) randomized controlled trial, (3) effects of saffron supplementation on depressive symptoms examined, and (4) study had either a placebo control or anti-depressant comparison group. DATA EXTRACTION AND ANALYSIS Using random effects modeling procedures, we calculated weighted mean effect sizes separately for the saffron supplementation vs. placebo control groups, and for the saffron supplementation vs. antidepressant groups. The methodological quality of all studies was assessed using the Jadad score. The computer software Comprehensive Meta-analysis 2 was used to analyze the data. RESULTS Based on our pre-specified criteria, five randomized controlled trials (n = 2 placebo controlled trials, n = 3 antidepressant controlled trials) were included in our review. A large effect size was found for saffron supplementation vs. placebo control in treating depressive symptoms (M ES

  16. Comparison between three types of stented pericardial aortic valves (Trivalve trial): study protocol for a randomized controlled trial

    PubMed Central

    2013-01-01

    Background Aortic valve stenosis is one of the most common heart diseases in older patients. Nowadays, surgical aortic valve replacement is the ‘gold standard’ treatment for this pathology and the most implanted prostheses are biological ones. The three most implanted bovine bioprostheses are the Trifecta valve (St. Jude Medical, Minneapolis, MN, USA), the Mitroflow valve (Sorin Group, Saluggia, Italy), and the Carpentier-Edwards Magna Ease valve (Edwards Lifesciences, Irvine, CA, USA). We propose a randomized trial to objectively assess the hemodynamic performances of these bioprostheses. Methods and design First, we will measure the aortic annulus diameter using CT-scan, echocardiography and by direct sizing in the operating room after native aortic valve resection. The accuracy of information, in terms of size and spatial dimensions of each bioprosthesis provided by manufacturers, will be checked. Their hemodynamic performances will be assessed postoperatively at the seventh day and the sixth month after surgery. Discussion This prospective controlled randomized trial aims to verify and compare the hemodynamic performances and the sizing of these three bioprostheses. The data obtained may help surgeons to choose the best suitable bioprosthesis according to each patient’s morphological characteristics. Trial registration ClinicalTrials.gov Identifier: NCT01522352 PMID:24299218

  17. Effects of zinc supplementation on subscales of anorexia in children: A randomized controlled trial

    PubMed Central

    Khademian, Majid; Farhangpajouh, Neda; Shahsanaee, Armindokht; Bahreynian, Maryam; Mirshamsi, Mehran; Kelishadi, Roya

    2014-01-01

    Objectives: This study aims to assess the effects of zinc supplementation on improving the appetite and its subscales in children. Methods: This study was conducted in 2013 in Isfahan, Iran. It had two phases. At the first step, after validation of the Child Eating Behaviour Questionaire (CEBQ), it was completed for 300 preschool children, who were randomly selected. The second phase was conducted as a randomized controlled trial. Eighty of these children were randomly selected, and were randomly assigned to two groups of equal number receiving zinc (10 mg/day) or placebo for 12 weeks. Results: Overall 77 children completed the trial (39 in the case and 3 in the control group).The results showed that zinc supplement can improve calorie intake in children by affecting some CEBQ subscales like Emotional over Eating and Food Responsible. Conclusion: Zinc supplementation had positive impact in promoting the calorie intake and some subscales of anorexia. PMID:25674110

  18. Effects of yoga on chronic neck pain: a systematic review of randomized controlled trials.

    PubMed

    Kim, Sang-Dol

    2016-07-01

    [Purpose] The aim of this study was to investigate the effectiveness of yoga in the management of chronic neck pain. [Subjects and Methods] Five electronic databases were searched to identify randomized controlled trials (RCTs) of yoga intervention on chronic neck pain. The trials were published in the English language between January 1966 and December 2015. The Cochrane Risk of Bias Tool was used to assess the quality of the trials. [Results] Three trials were identified and included in this review. A critical appraisal was performed on the trials, and the result indicated a high risk of bias. A narrative description was processed because of the small number of RCTs. Neck pain intensity and functional disability were significantly lower in the yoga groups than in the control groups. [Conclusion] Evidence from the 3 randomly controlled trials shows that yoga may be beneficial for chronic neck pain. The low-quality result of the critical appraisal and the small number of trials suggest that high-quality RCTs are required to examine further the effects of yoga intervention on chronic neck pain relief. PMID:27512290

  19. Effects of yoga on chronic neck pain: a systematic review of randomized controlled trials

    PubMed Central

    Kim, Sang-Dol

    2016-01-01

    [Purpose] The aim of this study was to investigate the effectiveness of yoga in the management of chronic neck pain. [Subjects and Methods] Five electronic databases were searched to identify randomized controlled trials (RCTs) of yoga intervention on chronic neck pain. The trials were published in the English language between January 1966 and December 2015. The Cochrane Risk of Bias Tool was used to assess the quality of the trials. [Results] Three trials were identified and included in this review. A critical appraisal was performed on the trials, and the result indicated a high risk of bias. A narrative description was processed because of the small number of RCTs. Neck pain intensity and functional disability were significantly lower in the yoga groups than in the control groups. [Conclusion] Evidence from the 3 randomly controlled trials shows that yoga may be beneficial for chronic neck pain. The low-quality result of the critical appraisal and the small number of trials suggest that high-quality RCTs are required to examine further the effects of yoga intervention on chronic neck pain relief. PMID:27512290

  20. Lessons Learned from EVOLVE for Planning of Future Randomized Trials in Patients on Dialysis.

    PubMed

    Parfrey, Patrick S; Block, Geoffrey A; Correa-Rotter, Ricardo; Drüeke, Tilman B; Floege, Jürgen; Herzog, Charles A; London, Gerard M; Mahaffey, Kenneth W; Moe, Sharon M; Wheeler, David C; Chertow, Glenn M

    2016-03-01

    The effect of the calcimimetic cinacalcet on cardiovascular disease in patients undergoing hemodialysis with secondary hyperparathyroidism was assessed in the Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events trial. This was the largest (in size) and longest (in duration) randomized controlled clinical trial undertaken in this population. During planning, execution, analysis, and reporting of the trial, many lessons were learned, including those related to the use of a composite cardiovascular primary endpoint, definition of endpoints (particularly heart failure and severe unremitting hyperparathyroidism), importance of age for optimal stratification at randomization, use of unadjusted and adjusted intention-to-treat analysis for the primary outcome, how to respond to a lower-than-predicted event rate during the trial, development of a prespecified analytic plan that accounted for nonadherence and for cointerventions that diminished the power of the trial to observe a treatment effect, determination of the credibility of a subgroup effect, use of adverse effects database to investigate rare diseases, collection of blood for biomarker measurement not designated before trial initiation, and interpretation of the benefits-to-harms ratio for individual patients. It is likely that many of these issues will arise in the planning of future trials in CKD. PMID:26614406

  1. Statistical Reviewers Improve Reporting in Biomedical Articles: A Randomized Trial

    PubMed Central

    Cobo, Erik; Selva-O'Callagham, Albert; Ribera, Josep-Maria; Cardellach, Francesc; Dominguez, Ruth; Vilardell, Miquel

    2007-01-01

    Background Although peer review is widely considered to be the most credible way of selecting manuscripts and improving the quality of accepted papers in scientific journals, there is little evidence to support its use. Our aim was to estimate the effects on manuscript quality of either adding a statistical peer reviewer or suggesting the use of checklists such as CONSORT or STARD to clinical reviewers or both. Methodology and Principal Findings Interventions were defined as 1) the addition of a statistical reviewer to the clinical peer review process, and 2) suggesting reporting guidelines to reviewers; with “no statistical expert” and “no checklist” as controls. The two interventions were crossed in a 2×2 balanced factorial design including original research articles consecutively selected, between May 2004 and March 2005, by the Medicina Clinica (Barc) editorial committee. We randomized manuscripts to minimize differences in terms of baseline quality and type of study (intervention, longitudinal, cross-sectional, others). Sample-size calculations indicated that 100 papers provide an 80% power to test a 55% standardized difference. We specified the main outcome as the increment in quality of papers as measured on the Goodman Scale. Two blinded evaluators rated the quality of manuscripts at initial submission and final post peer review version. Of the 327 manuscripts submitted to the journal, 131 were accepted for further review, and 129 were randomized. Of those, 14 that were lost to follow-up showed no differences in initial quality to the followed-up papers. Hence, 115 were included in the main analysis, with 16 rejected for publication after peer review. 21 (18.3%) of the 115 included papers were interventions, 46 (40.0%) were longitudinal designs, 28 (24.3%) cross-sectional and 20 (17.4%) others. The 16 (13.9%) rejected papers had a significantly lower initial score on the overall Goodman scale than accepted papers (difference 15.0, 95% CI: 4.6–24

  2. Adjuvant radiotherapy of regional lymph nodes in breast cancer - a meta-analysis of randomized trials

    PubMed Central

    2013-01-01

    Background Radiotherapy (RT) improves overall survival (OS) of breast cancer patients after breast conserving surgery and after mastectomy in patients with involved lymph nodes (LN). The contribution of RT to the regional LN to this survival benefit was poorly understood. Recently, the results of three large randomized trials addressing this question have become available. Material and methods The published abstracts (full publication pending) of the MA.20 (n=1832) and the EORTC 22922–10925 (EORTC) (n=4004) trial and the full publication of the French trial (n=1334) were basis of the meta-analysis. Main eligibility criteria were positive axillary LN (all trials), LN negative disease with high risk for recurrence (MA.20), and medial/central tumor location (French, EORTC). The MA.20 and the EORTC trial tested the effect of additional regional RT to the internal mammary (IM) LN and medial supraclavicular (MS) LN, whereas in the French trial all patients received RT to the MS-LN and solely RT to the IM-LN was randomized. Primary endpoint was OS. Secondary endpoints were disease-free survival (DFS) and distant metastasis free survival (DMFS). Results Regional RT of the MS-LN and the IM-LN (MA.20 and EORTC) resulted in a significant improvement of OS (Hazard Ratio (HR) 0.85 (95% CL 0.75 - 0.96)). Adding the results of the French trial and using the random effects model to respect the different design of the French trial, the effect on OS of regional radiotherapy was still significant (HR 0.88 (95% CL 0.80 - 0.97)). The absolute benefits in OS were 1.6% in the MA.20 trial at 5 years, 1.6% in the EORTC trial at 10 years, and 3.3% in the French trial at 10 years (not significant in single trials). Regional radiotherapy of the MS-LN and the IM-LN (MA.20 and EORTC) was associated with a significant improvement of DFS (HR 0.85 (95% CL 0.77 - 0.94)) and DMFS (HR 0.82 (95% CL 0.73 - 0.92)). The effect sizes were not significantly different between trials for any end point

  3. Using community readiness key informant assessments in a randomized group prevention trial: impact of a participatory community-media intervention.

    PubMed

    Slater, Michael D; Edwards, Ruth W; Plested, Barbara A; Thurman, Pamela J; Kelly, Kathleen J; Comello, Maria Leonora G; Keefe, Thomas J

    2005-02-01

    This study examines the role of key informant community readiness assessments in a randomized group trial testing the impact of a participatory community-media intervention (which was also complemented by in-school efforts). These assessments were used to help match communities in random assignment, as a source of formative data about the community, as the basis for a coalition-building workshop, and as an evaluation tool, with a follow-up set of surveys approximately 2 years after the baseline survey. Results of the nested, random effects analysis indicated that the intervention influenced community knowledge of efforts and (at marginally significant levels) improved prevention leadership quality and community climate supportive of prevention efforts. There was evidence that the professional affiliation of informants in some cases had an effect on their assessments, which could be controlled in the analysis. The authors conclude that key informant community readiness assessments can usefully serve to supplement aggregated measures of individual attitudes and behavior (reported elsewhere for this study) in evaluating community-based interventions. PMID:15751598

  4. A group-randomized tobacco trial among 30 Pacific Northwest colleges: Results from the Campus Health Action on Tobacco study

    PubMed Central

    McLerran, Dale; Livaudais, Jennifer C.; Coronado, Gloria D.

    2010-01-01

    Introduction: We conducted a group-randomized trial to increase smoking cessation and decrease smoking onset and prevalence in 30 colleges and universities in the Pacific Northwest. Methods: Random samples of students, oversampling for freshmen, were drawn from the participating colleges; students completed a questionnaire that included seven major areas of tobacco policies and behavior. Following this baseline, the colleges were randomized to intervention or control. Three interventionists developed Campus Advisory Boards in the 15 intervention colleges and facilitated intervention activities. The freshmen cohort was resurveyed 1 and 2 years after the baseline. Two-years postrandomization, new cross-sectional samples were drawn, and students were surveyed. Results: At follow-up, we found no significant overall differences between intervention and control schools when examining smoking cessation, prevalence, or onset. There was a significant decrease in prevalence in private independent colleges, a significant increase in cessation among rural schools, and a decrease in smoking onset in urban schools. Discussion: Intervention in this college population had mixed results. More work is needed to determine how best to reach this population of smokers. PMID:20447935

  5. Therapeutic alliance in a randomized clinical trial for bulimia nervosa

    PubMed Central

    Accurso, Erin C.; Fitzsimmons-Craft, Ellen E.; Ciao, Anna; Cao, Li; Crosby, Ross D.; Smith, Tracey L.; Klein, Marjorie H.; Mitchell, James E.; Crow, Scott J.; Wonderlich, Stephen A.; Peterson, Carol B.

    2015-01-01

    Objective This study examined the temporal relation between therapeutic alliance and outcome in two treatments for bulimia nervosa (BN). Method Eighty adults with BN symptoms were randomized to 21 sessions of integrative cognitive-affective therapy (ICAT) or enhanced cognitive-behavioral therapy (CBT-E). Bulimic symptoms (i.e., frequency of binge eating and purging) were assessed at each session and post-treatment. Therapeutic alliance (Working Alliance Inventory) was assessed at sessions 2, 8, 14, and post-treatment. Repeated-measures analyses using linear mixed models with random intercepts were conducted to determine differences in alliance growth by treatment and patient characteristics. Mixed-effects models examined the relation between alliance and symptom improvement. Results Overall, patients in both treatments reported strong therapeutic alliances. Regardless of treatment, greater therapeutic alliance between (but not within) subjects predicted greater reductions in bulimic behavior; reductions in bulimic behavior also predicted improved alliance. Patients with higher depression, anxiety, or emotion dysregulation had a stronger therapeutic alliance in CBT-E than ICAT, while those with more intimacy problems had greater improvement in therapeutic alliance in ICAT compared to CBT-E. Conclusions Therapeutic alliance has a unique impact on outcome, independent of the impact of symptom improvement on alliance. Within- and between-subject effects revealed that changes in alliance over time did not predict symptom improvement, but rather that individuals who had a stronger alliance overall had better bulimic symptom outcomes. These findings indicate that therapeutic alliance is an important predictor of outcome in the treatment of BN. PMID:25894667

  6. Best (but oft-forgotten) practices: designing, analyzing, and reporting cluster randomized controlled trials.

    PubMed

    Brown, Andrew W; Li, Peng; Bohan Brown, Michelle M; Kaiser, Kathryn A; Keith, Scott W; Oakes, J Michael; Allison, David B

    2015-08-01

    Cluster randomized controlled trials (cRCTs; also known as group randomized trials and community-randomized trials) are multilevel experiments in which units that are randomly assigned to experimental conditions are sets of grouped individuals, whereas outcomes are recorded at the individual level. In human cRCTs, clusters that are randomly assigned are typically families, classrooms, schools, worksites, or counties. With growing interest in community-based, public health, and policy interventions to reduce obesity or improve nutrition, the use of cRCTs has increased. Errors in the design, analysis, and interpretation of cRCTs are unfortunately all too common. This situation seems to stem in part from investigator confusion about how the unit of randomization affects causal inferences and the statistical procedures required for the valid estimation and testing of effects. In this article, we provide a brief introduction and overview of the importance of cRCTs and highlight and explain important considerations for the design, analysis, and reporting of cRCTs by using published examples. PMID:26016864

  7. Expected value of sample information for multi-arm cluster randomized trials with binary outcomes.

    PubMed

    Welton, Nicky J; Madan, Jason J; Caldwell, Deborah M; Peters, Tim J; Ades, Anthony E

    2014-04-01

    Expected value of sample information (EVSI) measures the anticipated net benefit gained from conducting new research with a specific design to add to the evidence on which reimbursement decisions are made. Cluster randomized trials raise specific issues for EVSI calculations because 1) a hierarchical model is necessary to account for between-cluster variability when incorporating new evidence and 2) heterogeneity between clusters needs to be carefully characterized in the cost-effectiveness analysis model. Multi-arm trials provide parameter estimates that are correlated, which needs to be accounted for in EVSI calculations. Furthermore, EVSI is computationally intensive when the net benefit function is nonlinear, due to the need for an inner-simulation step. We develop a method for the computation of EVSI that avoids the inner simulation step for cluster randomized multi-arm trials with a binary outcome, where the net benefit function is linear in the probability of an event but nonlinear in the log-odds ratio parameters. We motivate and illustrate the method with an example of a cluster randomized 2 × 2 factorial trial for interventions to increase attendance at breast screening in the UK, using a previously reported cost-effectiveness model. We highlight assumptions made in our approach, extensions to individually randomized trials and inclusion of covariates, and areas for further developments. We discuss computation time, the research-design space, and the ethical implications of an EVSI approach. We suggest that EVSI is a practical and appropriate tool for the design of cluster randomized trials. PMID:24085289

  8. A comparison between enriched and nonenriched enrollment randomized withdrawal trials of opioids for chronic noncancer pain

    PubMed Central

    Furlan, Andrea D; Chaparro, Luis E; Irvin, Emma; Mailis-Gagnon, Angela

    2011-01-01

    BACKGROUND: An enriched enrollment randomized withdrawal (EERW) design excludes potential participants who are nonresponders or who cannot tolerate the experimental drug before random assignment. It is unclear whether EERW design has an influence on the efficacy and safety of opioids for chronic noncancer pain (CNCP). OBJECTIVES: The primary objective was to compare the results from EERW and non-EERW trials of opioids for CNCP. Secondary objectives were to compare weak versus strong opioids, subgroups of patients with different types of pain, and the efficacy of opiods compared with placebo versus other drugs. METHODS: MEDLINE, EMBASE and CENTRAL were searched up to July 2009, for randomized controlled trials of any opioid for CNCP. Meta-analyses and meta-regressions were conducted to compare the results. Treatment efficacy was assessed by effect sizes (small, medium and large) and the incidence of adverse effects was assessed by a clinically relevant mean difference of 10% or greater. RESULTS: Sixty-two randomized trials were included. In 61 trials, the duration was less than 16 weeks. There was no difference in efficacy between EERW and non-EERW trials for both pain (P=0.6) and function (P=0.3). However, EERW trials failed to detect a clinically relevant difference for nausea, vomiting, somnolence, dizziness and dry skin/itching compared with non-EERW. Opioids were more effective than placebo in patients with nociceptive pain (effect size=0.60, 95% CI 0.49 to 0.72) and neuropathic pain (effect size=0.56, 95% CI 0.38 to 0.73). CONCLUSION: EERW trial designs appear not to bias the results of efficacy, but they underestimate the adverse effects. The present updated meta-analysis shows that weak and strong opioids are effective for CNCP of both nociceptive and neuropathic origin. PMID:22059206

  9. Robustness of ordinary least squares in randomized clinical trials.

    PubMed

    Judkins, David R; Porter, Kristin E

    2016-05-20

    There has been a series of occasional papers in this journal about semiparametric methods for robust covariate control in the analysis of clinical trials. These methods are fairly easy to apply on currently available computers, but standard software packages do not yet support these methods with easy option selections. Moreover, these methods can be difficult to explain to practitioners who have only a basic statistical education. There is also a somewhat neglected history demonstrating that ordinary least squares (OLS) is very robust to the types of outcome distribution features that have motivated the newer methods for robust covariate control. We review these two strands of literature and report on some new simulations that demonstrate the robustness of OLS to more extreme normality violations than previously explored. The new simulations involve two strongly leptokurtic outcomes: near-zero binary outcomes and zero-inflated gamma outcomes. Potential examples of such outcomes include, respectively, 5-year survival rates for stage IV cancer and healthcare claim amounts for rare conditions. We find that traditional OLS methods work very well down to very small sample sizes for such outcomes. Under some circumstances, OLS with robust standard errors work well with even smaller sample sizes. Given this literature review and our new simulations, we think that most researchers may comfortably continue using standard OLS software, preferably with the robust standard errors. PMID:26694758

  10. Randomized, Controlled Clinical Trial of Bilayer Ceramic and Metal-Ceramic Crown Performance

    PubMed Central

    Esquivel-Upshaw, Josephine; Rose, William; Oliveira, Erica; Yang, Mark; Clark, Arthur E.; Anusavice, Kenneth

    2013-01-01

    Purpose Analyzing the clinical performance of restorative materials is important, as there is an expectation that these materials and procedures will restore teeth and do no harm. The objective of this research study was to characterize the clinical performance of metal-ceramic crowns, core ceramic crowns, and core ceramic/veneer ceramic crowns based on 11 clinical criteria. Materials and Methods An IRB-approved, randomized, controlled clinical trial was conducted as a single-blind pilot study. The following three types of full crowns were fabricated: (1) metal-ceramic crown (MC) made from a Pd-Au-Ag-Sn-In alloy (Argedent 62) and a glass-ceramic veneer (IPS d.SIGN veneer); (2) non-veneered (glazed) lithium disilicate glass-ceramic crown (LDC) (IPS e.max Press core and e.max Ceram Glaze); and (3) veneered lithia disilicate glass-ceramic crown (LDC/V) with glass-ceramic veneer (IPS Empress 2 core and IPS Eris). Single-unit crowns were randomly assigned. Patients were recalled for each of 3 years and were evaluated by two calibrated clinicians. Thirty-six crowns were placed in 31 patients. A total of 12 crowns of each of the three crown types were studied. Eleven criteria were evaluated: tissue health, marginal integrity, secondary caries, proximal contact, anatomic contour, occlusion, surface texture, cracks/chips (fractures), color match, tooth sensitivity, and wear (of crowns and opposing enamel). Numerical rankings ranged from 1 to 4, with 4 being excellent, and 1 indicating a need for immediate replacement. Statistical analysis of the numerical rankings was performed using a Fisher’s exact test. Results There was no statistically significant difference between performance of the core ceramic crowns and the two veneered crowns at year 1 and year 2 (p > 0.05). All crowns were rated either as excellent or good for each of the clinical criteria; however, between years 2 and 3, gradual roughening of the occlusal surface occurred in some of the ceramic-ceramic crowns

  11. Brief Report: Staged-informed Consent in the Cohort Multiple Randomized Controlled Trial Design.

    PubMed

    Young-Afat, Danny A; Verkooijen, Helena A M; van Gils, Carla H; van der Velden, Joanne M; Burbach, Johannes P; Elias, Sjoerd G; van Delden, Jonannes J; Relton, Clare; van Vulpen, Marco; van der Graaf, Rieke

    2016-05-01

    The "cohort multiple randomized controlled trial," a new design for pragmatic trials, embeds multiple trials within a cohort. The cohort multiple RCT is an attractive alternative to conventional RCTs in fields where recruitment is slow, multiple new (competing) interventions for the same condition have to be tested, new interventions are highly preferred by patients and doctors, and the risk of disappointment bias, cross-over, and contamination is considerable. To prevent these unwanted effects, the cohort multiple RCT provides information on randomization to the intervention group/arm only, and only after randomization (i.e., prerandomization). To some, especially in a clinical setting, this is not ethically acceptable. In this article, we argue that prerandomization in the cohort multiple randomized controlled trial (cmRCT) can be avoided by adopting a staged-informed consent procedure. In the first stage, at entry into the cohort, all potential participants are asked for their informed consent to participate in a cohort study and broad consent to be either randomly selected to be approached for experimental interventions or to serve as control without further notice during participation in the cohort. In a second stage, at the initiation of an RCT within the cohort, informed consent to receive the intervention is then only sought in those randomly selected for the intervention arm. At the third stage, after completion of each RCT, all cohort participants receive aggregate disclosure of trial results. This staged-informed consent procedure avoids prerandomization in cmRCT and aims to keep participants actively engaged in the research process. PMID:27035689

  12. Randomized trials published in Chinese or Western journals: comparative empirical analysis.

    PubMed

    Purgato, Marianna; Cipriani, Andrea; Barbui, Corrado

    2012-06-01

    A major concern to the inclusion in systematic reviews of studies originating in China and published in Chinese journals refers to the quality of study reporting. In this systematic survey of randomized trials, we compared the characteristics of studies published in Chinese journals with those of studies published in Western journals. We included 69 studies comparing citalopram with other antidepressant drugs in the treatment of major depression. Of these, 37 (54%) were published in Chinese journals. The standard of reporting was generally poor in both Western and Chinese studies. In some Chinese studies, the generation of the randomization sequence raised concern about their experimental nature, and in almost all included studies, the concealment of allocation was not properly described. Blinding was seldom adopted in Chinese studies, and the risk of sponsorship bias was uncertain because Chinese studies did not report any financial support. In most Western studies, outcome data were selectively and incompletely reported. Pooling together all trials revealed that citalopram was similarly effective in comparison with all other antidepressant drugs both in Western studies (standardized mean difference, -0.04; 95% confidence interval, -0.15 to 0.06) and in Chinese studies (standardized mean difference, -0.08, 95% confidence interval, -0.18 to 0.02). Randomized controlled trials published in Chinese journals represent most of the studies included in this review. This suggests that omitting to search biomedical databases originating from China would systematically exclude a relevant proportion of randomized trials published in Chinese journals, with a risk of random error or bias. The increasing inclusion of Chinese studies in systematic reviews reinforces the need to check the quality of randomized trials that are meta-analyzed. PMID:22544018

  13. Effects of Source- versus Household Contamination of Tubewell Water on Child Diarrhea in Rural Bangladesh: A Randomized Controlled Trial

    PubMed Central

    Unicomb, Leanne; Arnold, Benjamin F.; Colford Jr., John M.; Luby, Stephen P.

    2015-01-01

    Background Shallow tubewells are the primary drinking water source for most rural Bangladeshis. Fecal contamination has been detected in tubewells, at low concentrations at the source and at higher levels at the point of use. We conducted a randomized controlled trial to assess whether improving the microbiological quality of tubewell drinking water by household water treatment and safe storage would reduce diarrhea in children <2 years in rural Bangladesh. Methods We randomly assigned 1800 households with a child aged 6-18 months (index child) into one of three arms: chlorine plus safe storage, safe storage and control. We followed households with monthly visits for one year to promote the interventions, track their uptake, test participants’ source and stored water for fecal contamination, and record caregiver-reported child diarrhea prevalence (primary outcome). To assess reporting bias, we also collected data on health outcomes that are not expected to be impacted by our interventions. Findings Both interventions had high uptake. Safe storage, alone or combined with chlorination, reduced heavy contamination of stored water. Compared to controls, diarrhea in index children was reduced by 36% in the chlorine plus safe storage arm (prevalence ratio, PR = 0.64, 0.55-0.73) and 31% in the safe storage arm (PR = 0.69, 0.60-0.80), with no difference between the two intervention arms. One limitation of the study was the non-blinded design with self-reported outcomes. However, the prevalence of health outcomes not expected to be impacted by water interventions did not differ between study arms, suggesting minimal reporting bias. Conclusions Safe storage significantly improved drinking water quality at the point of use and reduced child diarrhea in rural Bangladesh. There was no added benefit from combining safe storage with chlorination. Efforts should be undertaken to implement and evaluate long-term efforts for safe water storage in Bangladesh. Trial Registration

  14. A participatory and capacity-building approach to healthy eating and physical activity – SCIP-school: a 2-year controlled trial

    PubMed Central

    2012-01-01

    Background Schools can be effective settings for improving eating habits and physical activity, whereas it is more difficult to prevent obesity. A key challenge is the “implementation gap”. Trade-off must be made between expert-driven programmes on the one hand and contextual relevance, flexibility, participation and capacity building on the other. The aim of the Stockholm County Implementation Programme was to improve eating habits, physical activity, self-esteem, and promote a healthy body weight in children aged 6–16 years. We describe the programme, intervention fidelity, impacts and outcomes after two years of intervention. Methods Nine out of 18 schools in a middle-class municipality in Sweden agreed to participate whereas the other nine schools served as the comparison group (quasi-experimental study). Tailored action plans were developed by school health teams on the basis of a self-assessment questionnaire called KEY assessing strengths and weaknesses of each school’s health practices and environments. Process evaluation was carried out by the research staff. Impacts at school level were assessed yearly by the KEY. Outcome measures at student level were anthropometry (measured), and health behaviours assessed by a questionnaire, at baseline and after 2 years. All children in grade 2, 4 and 7 were invited to participate (n=1359) of which 59.8% consented. The effect of the intervention on health behaviours, self-esteem, weight status and BMIsds was evaluated by unilevel and multilevel regression analysis adjusted for gender and baseline values. Results Programme fidelity was high demonstrating feasibility, but fidelity to school action plans was only 48% after two years. Positive and significant (p<.05) impacts were noted in school health practices and environments after 2 years. At student level no significant intervention effects were seen for the main outcomes. Conclusions School staff has the capacity to create their own solutions and make

  15. Randomized trial of tacrolimus versus cyclosporin microemulsion in renal transplantation.

    PubMed

    Trompeter, Richard; Filler, Guido; Webb, Nicholas J A; Watson, Alan R; Milford, David V; Tyden, Gunnar; Grenda, Ryszard; Janda, Jan; Hughes, David; Ehrich, Jochen H H; Klare, Bernd; Zacchello, Graziella; Bjorn Brekke, Inge; McGraw, Mary; Perner, Ferenc; Ghio, Lucian; Balzar, Egon; Friman, Styrbjörn; Gusmano, Rosanna; Stolpe, Jochen

    2002-03-01

    This study was undertaken to compare the efficacy and safety of tacrolimus (Tac) with the microemulsion formulation of cyclosporin (CyA) in children undergoing renal transplantation. A 6-month, randomized, prospective, open, parallel group study with an open extension phase was conducted in 18 centers from nine European countries. In total, 196 pediatric patients (<18 years) were randomly assigned (1:1) to receive either Tac ( n=103) or CyA microemulsion ( n=93) administered concomitantly with azathioprine and corticosteroids. The primary endpoint was incidence and time to first acute rejection. Baseline characteristics were comparable between treatment groups. Tac therapy resulted in a significantly lower incidence of acute rejection (36.9%) compared with CyA therapy (59.1%) ( P=0.003). The incidence of corticosteroid-resistant rejection was also significantly lower in the Tac group compared with the CyA group (7.8% vs. 25.8%, P=0.001). The differences were also significant for biopsy-confirmed acute rejection (16.5% vs. 39.8%, P<0.001). At 1 year, patient survival was similar (96.1% vs. 96.6%), while 10 grafts were lost in the Tac group compared with 17 graft losses in the CyA group ( P=0.06). At 1 year, mean glomerular filtration rate (Schwartz estimate) was significantly higher in the Tac group (62+/-20 ml/min per 1.73 m(2), n=84) than in the CyA group (56+/-21 ml/min per 1.73 m(2), n=74, P=0.03). The most frequent adverse events during the first 6 months were hypertension (68.9% vs. 61.3%), hypomagnesemia (34.0% vs. 12.9%, P=0.001), and urinary tract infection (29.1% vs. 33.3%). Statistically significant differences ( P<0.05) were observed for diarrhea (13.6% vs. 3.2%), hypertrichosis (0.0% vs. 7.5%), flu syndrome (0.0% vs. 5.4%), and gum hyperplasia (0.0% vs. 5.4%). In previously non-diabetic children, the incidence of long-term (>30 days) insulin use was 3.0% (Tac) and 2.2% (CyA). Post-transplant lymphoproliferative disease was observed in 1 patient in the

  16. The chronic autoimmune thyroiditis quality of life selenium trial (CATALYST): study protocol for a randomized controlled trial

    PubMed Central

    2014-01-01

    Background Patients with chronic autoimmune thyroiditis have impaired health-related quality of life. The thyroid gland has a high selenium concentration, and specific selenoprotein enzyme families are crucial to immune function, and catalyze thyroid hormone metabolism and redox processes in thyroid cells. Previous randomized controlled trials have found that selenium supplementation decreases thyroid-disease-specific antibody levels. We hypothesize that selenium might be beneficial in the treatment of chronic autoimmune thyroiditis. Methods/Design The CATALYST trial is an investigator-initiated randomized, blinded, multicentre clinical trial of selenium supplementation versus placebo in patients with chronic autoimmune thyroiditis. Inclusion criteria: age ≥18 years; serum thyroid peroxidase antibody level ≥100 IU/ml within the previous 12 months; treatment with levothyroxine and written informed consent. Exclusion criteria: previous diagnosis of toxic nodular goitre, Graves’ hyperthyroidism, postpartum thyroiditis, Graves’ orbitopathy; previous antithyroid drug treatment, radioiodine therapy or thyroid surgery; immune-modulatory or other medication affecting thyroid function; pregnancy, planned pregnancy or breastfeeding; allergy towards any intervention or placebo component; intake of selenium supplementation >55 μg/day; inability to read or understand Danish or lack of informed consent. The trial will include 2 × 236 participants. The experimental intervention and control groups will receive 200 μg selenium-enriched yeast or matching placebo tablets daily for 12 months. The experimental supplement will be SelenoPrecise®. The primary outcome is thyroid-related quality of life assessed by the Thyroid Patient-Reported Outcome (ThyPRO) questionnaire. Secondary outcomes include serum thyroid peroxidase antibody concentration; serum triiodothyronine/thyroxine ratio; levothyroxine dosage; adverse reactions and serious adverse reactions and events

  17. A randomized trial of an interim methadone maintenance clinic.

    PubMed Central

    Yancovitz, S R; Des Jarlais, D C; Peyser, N P; Drew, E; Friedmann, P; Trigg, H L; Robinson, J W

    1991-01-01

    BACKGROUND. Interim methadone maintenance has been proposed as a method of providing clinically effective services to heroin addicts waiting for treatment in standard comprehensive methadone maintenance programs. METHODS. A clinic that provided initial medical evaluation, methadone medication, and AIDS education, but did not include formal drug abuse counseling or other social support services was established in New York City. A sample of 301 volunteer subjects recruited from the waiting list for treatment in the Beth Israel methadone program were randomly assigned to immediate entry into the interim clinic or a control group. RESULTS. There were no differences in initial levels of illicit drug use across the experimental and control groups. One-month urinalysis follow-up data showed a significant reduction in heroin use in the experimental group (from 63% positive at intake to 29% positive) with no change in the control group (62% to 60% positive). No significant change was observed in cocaine urinalyses (approximately 70% positive for both groups at intake and follow-up). A higher percentage of the experimental group were in treatment at 16-month follow-up (72% vs 56%). CONCLUSIONS. Limited services interim methadone maintenance can reduce heroin use among persons awaiting entry into comprehensive treatment and increase the percentage entering treatment. PMID:1659236

  18. Prize Contingency Management for Smoking Cessation: A Randomized Trial

    PubMed Central

    Ledgerwood, David M.; Arfken, Cynthia L.; Petry, Nancy M.; Alessi, Sheila M.

    2016-01-01

    Background Adjunctive behavioral smoking cessation treatments have the potential to improve outcomes beyond standard care. The present study had two aims: 1) compare standard care (SC) for smoking (four weeks of brief counseling and monitoring) to SC plus prize-based contingency management (CM), involving the chance to earn prizes on days with demonstrated smoking abstinence (carbon monoxide (CO) ≤6ppm); and 2) compare the relative efficacy of two prize reinforcement schedules - one a traditional CM schedule, and the second an early enhanced CM schedule providing greater reinforcement magnitude in the initial week of treatment but equal overall reinforcement. Methods Participants (N = 81 nicotine-dependent cigarette smokers) were randomly assigned to one of the three conditions. Results Prize CM resulted in significant reductions in cigarette smoking relative to SC. These reductions were not apparent at follow-up. We found no meaningful differences between the traditional and enhanced CM conditions. Conclusions Our findings reveal that prize CM leads to significant reductions in smoking during treatment relative to a control intervention, but the benefits did not extend long-term. PMID:24793364

  19. Brief cognitive therapy for panic disorder: a randomized controlled trial.

    PubMed

    Clark, D M; Salkovskis, P M; Hackmann, A; Wells, A; Ludgate, J; Gelder, M

    1999-08-01

    Cognitive therapy (CT) is a specific and highly effective treatment for panic disorder (PD). Treatment normally involves 12-15 1-hr sessions. In an attempt to produce a more cost-effective version, a briefer treatment that made extensive use of between-sessions patient self-study modules was created. Forty-three PD patients were randomly allocated to full CT (FCT), brief CT (BCT), or a 3-month wait list. FCT and BCT were superior to wait list on all measures, and the gains obtained in treatment were maintained at 12-month follow-up. There were no significant differences between FCT and BCT. Both treatments had large (approximately 3.0) and essentially identical effect sizes. BCT required 6.5 hr of therapist time, including booster sessions. Patients' initial expectation of therapy success was negatively correlated with posttreatment panic-anxiety. Cognitive measures at the end of treatment predicted panic-anxiety at 12-month follow-up. PMID:10450630

  20. A randomized trial of telemonitoring heart failure patients.

    PubMed

    Tompkins, Christopher; Orwat, John

    2010-01-01

    The purpose of this study was to measure the ability of telemonitoring to reduce hospital days and total costs for Medicare managed care enrollees diagnosed with heart failure. Patients were recruited and randomly assigned for six months to either telemonitoring or standard care. Telemonitoring transmitted vital signs and clinical alerts daily to a central nursing station. Utilization of covered services was analyzed for the six-month telemonitoring period to test for hypothesized reductions in hospital days and changes in utilization of the emergency department (ED), urgent care, and primary care. Negative binomial regressions adjusted for gender, age, co-occurring diabetes, co-occurring chronic obstructive pulmonary disease, and residence neighborhood were used to analyze units of service, and two-part (hurdle) multivariable models were used for expenditures. The main finding was a tendency for lower total number of hospital days for patients assigned to telemonitoring. Results for other covered services were generally consistent with hypothesized direction and magnitude; however, statistical power was reduced because of lower-than-expected recruitment rates into the study. Within a managed-care environment, telemonitoring appears to facilitate better ambulatory management of heart failure patients, including fewer ED visits, which were offset by more frequent primary care and urgent care visits. PMID:21077581

  1. Computerized dental injection fear treatment: a randomized clinical trial.

    PubMed

    Heaton, L J; Leroux, B G; Ruff, P A; Coldwell, S E

    2013-07-01

    One in four adults reports a clinically significant fear of dental injections, leading many to avoid dental care. While systematic desensitization is the most common therapeutic method for treating specific phobias such as fear of dental injections, lack of access to trained therapists, as well as dentists' lack of training and time in providing such a therapy, means that most fearful individuals are not able to receive the therapy needed to be able to receive necessary dental treatment. Computer Assisted Relaxation Learning (CARL) is a self-paced computerized treatment based on systematic desensitization for dental injection fear. This multicenter, block-randomized, dentist-blind, parallel-group study conducted in 8 sites in the United States compared CARL with an informational pamphlet in reducing fear of dental injections. Participants completing CARL reported significantly greater reduction in self-reported general and injection-specific dental anxiety measures compared with control individuals (p < .001). Twice as many CARL participants (35.3%) as controls (17.6%) opted to receive a dental injection after the intervention, although this was not statistically significant. CARL, therefore, led to significant changes in self-reported fear in study participants, but no significant differences in the proportion of participants having a dental injection. PMID:23690352

  2. Self-monitoring of reexperiencing symptoms: a randomized trial.

    PubMed

    Brown, Amanda Joelle; Bollini, Annie M; Craighead, Linda W; Astin, Millie C; Norrholm, Seth Davin; Bradley, Bekh

    2014-10-01

    The efficacy of a brief intervention to self-monitor reexperiencing symptoms was evaluated in 137 U.S. combat veterans with PTSD who were enrolled in 5-week psychoeducation groups at a large Veterans Affairs Medical Center. Groups were randomized to psychoeducation alone (Education Control, n = 50) or psychoeducation plus intrusion monitoring (Education + Monitoring, n = 87). Education + Monitoring participants were asked to make a daily record of the number and content of nightmares, flashbacks, intrusive trauma-related thoughts, and physiological and emotional reactions to triggers. Avoidance symptoms were reduced in both conditions (η(2)  = .093), with no additional benefit from intrusion monitoring (η(2)  = .001). Compliance with intrusion monitoring was markedly low, which complicated the interpretation of the study findings. Even though intrusion monitoring has a strong theoretical foundation and may be an efficient and cost-effective alternative to more structured treatments for PTSD, the effect of intrusion monitoring will not be clearly understood until higher compliance can be achieved. Future work in this area should address barriers to compliance and investigate strategies for enhancing motivation to engage in self-monitoring. PMID:25322881

  3. Citalopram Intervention for Hostility: Results of a Randomized Clinical Trial

    PubMed Central

    Kamarck, Thomas W.; Haskett, Roger F.; Muldoon, Matthew; Flory, Janine D.; Anderson, Barbara; Bies, Rob; Pollock, Bruce; Manuck, Stephen B.

    2009-01-01

    Hostility is associated with an increased risk for cardiovascular disease (CVD). Because central serotonin may modulate aggression, we might expect selective serotonin reuptake inhibitors (SSRIs) to be effective in reducing hostility. Such effects have never been examined in individuals scoring high on hostility who are otherwise free from major DSM-IV Axis I psychopathology. 159 participants (ages 30–50, 50 % female) scoring high on 2 measures of hostility and with no current major Axis I diagnosis were randomly assigned to 2 months of citalopram (40 mg, fixed flexible dose) or placebo. Adherence was assessed by electronic measurement and by drug exposure assessment. Treated subjects showed larger reductions in state anger (condition-by-time p = .01), hostile affect (p = 02), and, among women only, physical and verbal aggression (p = .005) relative to placebo controls. Treatment was also associated with relative increases in perceived social support (p = .04). Findings have implications for understanding the CNS correlates of hostility, its associations with other psychosocial risk factors for CVD, and, potentially, for the design of effective interventions. PMID:19170463

  4. Carnosine Treatment for Gulf War Illness: A Randomized Controlled Trial

    PubMed Central

    Baraniuk, James N.; El-Amin, Suliman; Corey, Rebecca; Rayhan, Rakib U.; Timbol, Christian R.

    2013-01-01

    About 25% of 1990-1991 Persian Gulf War veterans experience disabling fatigue, widespread pain, and cognitive dysfunction termed Gulf War illness (GWI) or Chronic Multisymptom Illness (CMI). A leading theory proposes that wartime exposures initiated prolonged production of reactive oxygen species (ROS) and central nervous system injury. The endogenous antioxidant L-carnosine (β-alanyl-L-histidine) is a potential treatment since it is a free radical scavenger in nervous tissue. To determine if nutritional supplementation with L-carnosine would significantly improve pain, cognition and fatigue in GWI, a randomized double blind placebo controlled 12 week dose escalation study involving 25 GWI subjects was employed. L-carnosine was given as 500, 1000, and 1500 mg increasing at 4 week intervals. Outcomes included subjective fatigue, pain and psychosocial questionnaires, and instantaneous fatigue and activity levels recorded by ActiWatch Score devices. Cognitive function was evaluated by WAIS-R digit symbol substitution test. Carnosine had 2 potentially beneficial effects: WAIS-R scores increased significantly, and there was a decrease in diarrhea associated with irritable bowel syndrome. No other significant incremental changes were found. Therefore, 12 weeks of carnosine (1500 mg) may have beneficial cognitive effects in GWI. Fatigue, pain, hyperalgesia, activity and other outcomes were resistant to treatment. PMID:23618477

  5. Carnosine treatment for gulf war illness: a randomized controlled trial.

    PubMed

    Baraniuk, James Nicholas; El-Amin, Suliman; Corey, Rebecca; Rayhan, Rakib; Timbol, Christian

    2013-05-01

    About 25% of 1990-1991 Persian Gulf War veterans experience disabling fatigue, widespread pain, and cognitive dysfunction termed Gulf War illness (GWI) or Chronic Multisymptom Illness (CMI). A leading theory proposes that wartime exposures initiated prolonged production of reactive oxygen species (ROS) and central nervous system injury. The endogenous antioxidant L-carnosine (B-alanyl-L-histidine) is a potential treatment since it is a free radical scavenger in nervous tissue. To determine if nutritional supplementation with L-carnosine would significantly improve pain, cognition and fatigue in GWI, a randomized double blind placebo controlled 12 week dose escalation study involving 25 GWI subjects was employed. L-carnosine was given as 500, 1000, and 1500 mg increasing at 4 week intervals. Outcomes included subjective fatigue, pain and psychosocial questionnaires, and instantaneous fatigue and activity levels recorded by ActiWatch Score devices. Cognitive function was evaluated by WAIS-R digit symbol substitution test. Carnosine had 2 potentially beneficial effects: WAIS-R scores increased significantly, and there was a decrease in diarrhea associated with irritable bowel syndrome. No other significant incremental changes were found. Therefore, 12 weeks of carnosine (1500 mg) may have beneficial cognitive effects in GWI. Fatigue, pain, hyperalgesia, activity and other outcomes were resistant to treatment. PMID:23618477

  6. Nurse Family Partnership: Comparing Costs per Family in Randomized Trials Versus Scale-Up.

    PubMed

    Miller, Ted R; Hendrie, Delia

    2015-12-01

    The literature that addresses cost differences between randomized trials and full-scale replications is quite sparse. This paper examines how costs differed among three randomized trials and six statewide scale-ups of nurse family partnership (NFP) intensive home visitation to low income first-time mothers. A literature review provided data on pertinent trials. At our request, six well-established programs reported their total expenditures. We adjusted the costs to national prices based on mean hourly wages for registered nurses and then inflated them to 2010 dollars. A centralized data system provided utilization. Replications had fewer home visits per family than trials (25 vs. 31, p = .05), lower costs per client ($8860 vs. $12,398, p = .01), and lower costs per visit ($354 vs. $400, p = .30). Sample size limited the significance of these differences. In this type of labor intensive program, costs probably were lower in scale-up than in randomized trials. Key cost drivers were attrition and the stable caseload size possible in an ongoing program. Our estimates reveal a wide variation in cost per visit across six state programs, which suggests that those planning replications should not expect a simple rule to guide cost estimations for scale-ups. Nevertheless, NFP replications probably achieved some economies of scale. PMID:26507844

  7. A Randomized Controlled Trial of Koru: A Mindfulness Program for College Students and Other Emerging Adults

    ERIC Educational Resources Information Center

    Greeson, Jeffrey M.; Juberg, Michael K.; Maytan, Margaret; James, Kiera; Rogers, Holly

    2014-01-01

    Objective: To evaluate the effectiveness of Koru, a mindfulness training program for college students and other emerging adults. Participants: Ninety students (66% female, 62% white, 71% graduate students) participated between Fall 2012 and Spring 2013. Methods: Randomized controlled trial. It was hypothesized that Koru, compared with a wait-list…

  8. Thinking outside the Randomized Controlled Trials Experimental Box: Strategies for Enhancing Credibility and Social Justice

    ERIC Educational Resources Information Center

    Hesse-Biber, Sharlene

    2013-01-01

    Some evaluators employ randomized controlled trials (RCTs) as the gold standard of evidence-based practice (EBP). Critics of RCT designs argue that RCTs do not include the complexity of program participants' experiences or clinical expertise, and couple this with criticisms that it is difficult to transfer RCT findings from the laboratory to…

  9. Efficacy and safety of acupuncture for chronic dizziness: study protocol for a randomized controlled trial

    PubMed Central

    2013-01-01

    Background Dizziness is one of the most challenging symptoms in medicine. No medication for dizziness in current use has well-established curative or prophylactic value or is suitable for long-term palliative use. Unconventional remedies, such as acupuncture, should be considered and scientifically evaluated. However, there has been relatively little evidence in randomized controlled clinical trials on acupuncture to treat chronic dizziness. The aim of our study is to evaluate the efficacy and safety of acupuncture in patients with dizziness. Methods/Design This trial is a randomized, single-blind, controlled study. A total of 80 participants will be randomly assigned to two treatment groups receiving acupuncture and sham acupuncture treatment, respectively, for 4 weeks. The primary outcome measures are the Dizziness Handicap Inventory (DHI) and the Vertigo Symptom Scale (VSS). Treatment will be conducted over a period of 4 weeks, at a frequency of two sessions per week. The assessment is at baseline (before treatment initiation), 4 weeks after the first acupuncture session, and 8 weeks after the first acupuncture session. Discussion The results from this study will provide clinical evidence on the efficacy and safety of acupuncture in patients with chronic dizziness. Trial registration International Standard Randomized Controlled Trial Number Register: ISRCTN52695239 PMID:24330810

  10. The Role of Treatment Fidelity on Outcomes during a Randomized Field Trial of an Autism Intervention

    ERIC Educational Resources Information Center

    Mandell, David S; Stahmer, Aubyn C; Shin, Sujie; Xie, Ming; Reisinger, Erica; Marcus, Steven C

    2013-01-01

    This randomized field trial comparing Strategies for Teaching based on Autism Research and Structured Teaching enrolled educators in 33 kindergarten-through-second-grade autism support classrooms and 119 students, aged 5-8 years in the School District of Philadelphia. Students were assessed at the beginning and end of the academic year using the…

  11. Testing Mediators of Intervention Effects in Randomized Controlled Trials: An Evaluation of Three Depression Prevention Programs

    ERIC Educational Resources Information Center

    Stice, Eric; Rohde, Paul; Seeley, John R.; Gau, Jeff M.

    2010-01-01

    Objective: Evaluate a new 5-step method for testing mediators hypothesized to account for the effects of depression prevention programs. Method: In this indicated prevention trial, at-risk teens with elevated depressive symptoms were randomized to a group cognitive-behavioral (CB) intervention, group supportive expressive intervention, CB…

  12. Considerations for Designing Group Randomized Trials of Professional Development with Teacher Knowledge Outcomes

    ERIC Educational Resources Information Center

    Kelcey, Ben; Phelps, Geoffrey

    2013-01-01

    Despite recent shifts in research emphasizing the value of carefully designed experiments, the number of studies of teacher professional development with rigorous designs has lagged behind its student outcome counterparts. We outline a framework for the design of group randomized trials (GRTs) with teachers' knowledge as the outcome and…

  13. Multisite Randomized Controlled Trial Examining Intelligent Tutoring of Structure Strategy for Fifth-Grade Readers

    ERIC Educational Resources Information Center

    Wijekumar, Kausalai; Meyer, Bonnie J. F.; Lei, Pui-Wa; Lin, Yu-Chu; Johnson, Lori A.; Spielvogel, James A.; Shurmatz, Kathryn M.; Ray, Melissa; Cook, Michael

    2014-01-01

    This article reports on a large scale randomized controlled trial to study the efficacy of a web-based intelligent tutoring system for the structure strategy designed to improve content area reading comprehension. The research was conducted with 128 fifth-grade classrooms within 12 school districts in rural and suburban settings. Classrooms within…

  14. Randomized Controlled Trial of a Family Cognitive-Behavioral Preventive Intervention for Children of Depressed Parents

    ERIC Educational Resources Information Center

    Compas, Bruce E.; Forehand, Rex; Keller, Gary; Champion, Jennifer E.; Rakow, Aaron; Reeslund, Kristen L.; McKee, Laura; Fear, Jessica M.; Colletti, Christina J. M.; Hardcastle, Emily; Merchant, Mary Jane; Roberts, Lori; Potts, Jennifer; Garai, Emily; Coffelt, Nicole; Roland, Erin; Sterba, Sonya K.; Cole, David A.

    2009-01-01

    A family cognitive-behavioral preventive intervention for parents with a history of depression and their 9-15-year-old children was compared with a self-study written information condition in a randomized clinical trial (n = 111 families). Outcomes were assessed at post-intervention (2 months), after completion of 4 monthly booster sessions (6…

  15. An Empirical Comparison of Randomized Control Trials and Regression Discontinuity Estimations

    ERIC Educational Resources Information Center

    Barrera-Osorio, Felipe; Filmer, Deon; McIntyre, Joe

    2014-01-01

    Randomized controlled trials (RCTs) and regression discontinuity (RD) studies both provide estimates of causal effects. A major difference between the two is that RD only estimates local average treatment effects (LATE) near the cutoff point of the forcing variable. This has been cited as a drawback to RD designs (Cook & Wong, 2008).…

  16. Training Anxious Children to Disengage Attention from Threat: A Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Bar-Haim, Yair; Morag, Inbar; Glickman, Shlomit

    2011-01-01

    Background: Threat-related attention biases have been implicated in the etiology and maintenance of anxiety disorders. As a result, attention bias modification (ABM) protocols have been employed as treatments for anxious adults. However, they have yet to emerge for children. A randomized, double-blind placebo-controlled trial was conducted to…

  17. Interpretation Training in Individuals with Generalized Social Anxiety Disorder: A Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Amir, Nader; Taylor, Charles T.

    2012-01-01

    Objective: To examine the efficacy of a multisession computerized interpretation modification program (IMP) in the treatment of generalized social anxiety disorder (GSAD). Method: The sample comprised 49 individuals meeting diagnostic criteria for GSAD who were enrolled in a randomized, double-blind placebo-controlled trial comparing IMP (n = 23)…

  18. Bibliotherapy for Children with Anxiety Disorders Using Written Materials for Parents: A Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Rapee, Ronald M.; Abbott, Maree J.; Lyneham, Heidi J.

    2006-01-01

    The current trial examined the value of modifying empirically validated treatment for childhood anxiety for application via written materials for parents of anxious children. Two hundred sixty-seven clinically anxious children ages 6-12 years and their parents were randomly allocated to standard group treatment, wait list, or a bibliotherapy…

  19. Digestive Enzyme Supplementation for Autism Spectrum Disorders: A Double-Blind Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Munasinghe, Sujeeva A.; Oliff, Carolyn; Finn, Judith; Wray, John A.

    2010-01-01

    To examine the effects of a digestive enzyme supplement in improving expressive language, behaviour and other symptoms in children with Autism Spectrum Disorder. Randomized, double-blind placebo-controlled trial using crossover design over 6 months for 43 children, aged 3-8 years. Outcome measurement tools included monthly Global Behaviour Rating…

  20. Mixed Results from Six Large Randomized Controlled Trials of Learning Communities in Community Colleges

    ERIC Educational Resources Information Center

    Mayer, Alexander K.; Weiss, Michael J.; Visher, Mary G.; Sommo, Colleen; Rudd, Timothy; Cullinan, Dan; Weissman, Evan; Wathington, Heather D.

    2013-01-01

    This paper presents research that explores similarities and differences across six randomized controlled trials of learning communities in community colleges that were conducted by MDRC and the National Center for Postsecondary Research. Five of these studies track students' progress in the program semester and two follow-up semesters, and one…

  1. Randomized Trial of Continuing Care Enhancements for Cocaine-Dependent Patients following Initial Engagement

    ERIC Educational Resources Information Center

    McKay, James R.; Lynch, Kevin G.; Coviello, Donna; Morrison, Rebecca; Cary, Mark S.; Skalina, Lauren; Plebani, Jennifer

    2010-01-01

    Objective: The effects of cognitive-behavioral relapse prevention (RP), contingency management (CM), and their combination (CM + RP) were evaluated in a randomized trial with 100 cocaine-dependent patients (58% female, 89% African American) who were engaged in treatment for at least 2 weeks and had an average of 44 days of abstinence at baseline.…

  2. Explaining Feast or Famine in Randomized Field Trials: Medical Science and Criminology Compared.

    ERIC Educational Resources Information Center

    Shepherd, Jonathan P.

    2003-01-01

    Discusses the contrast between the frequency of randomized clinical trials in the health sciences and the relative famine of such studies in criminology. Attributes this difference to the contexts in which research is done and the difference in the status of situational research in the two disciplines. (SLD)

  3. Randomized, Controlled Trial of a Comprehensive Program for Young Students with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Young, Helen E.; Falco, Ruth A.; Hanita, Makoto

    2016-01-01

    This randomized, controlled trial, comparing the Comprehensive Autism Program (CAP) and business as usual programs, studied outcomes for 3-5 year old students with autism spectrum disorder (ASD). Participants included 84 teachers and 302 students with ASD and their parents. CAP utilized specialized curricula and training components to implement…

  4. Learning Mathematics in a Visuospatial Format: A Randomized, Controlled Trial of Mental Abacus Instruction

    ERIC Educational Resources Information Center

    Barner, David; Alvarez, George; Sullivan, Jessica; Brooks, Neon; Srinivasan, Mahesh; Frank, Michael C.

    2016-01-01

    Mental abacus (MA) is a technique of performing fast, accurate arithmetic using a mental image of an abacus; experts exhibit astonishing calculation abilities. Over 3 years, 204 elementary school students (age range at outset: 5-7 years old) participated in a randomized, controlled trial to test whether MA expertise (a) can be acquired in standard…

  5. Modified Constraint-Induced Therapy for Children with Hemiplegic Cerebral Palsy: A Randomized Trial

    ERIC Educational Resources Information Center

    Wallen, Margaret; Ziviani, Jenny; Naylor, Olivia; Evans, Ruth; Novak, Iona; Herbert, Robert D.

    2011-01-01

    Aim: Conventional constraint-based therapies are intensive and demanding to implement, particularly for children. Modified forms of constraint-based therapies that are family-centred may be more acceptable and feasible for families of children with cerebral palsy (CP)-but require rigorous evaluation using randomized trials. The aim of this study…

  6. Sibling Outcomes from a Randomized Trial of Evidence-Based Treatments with Substance Abusing Juvenile Offenders

    ERIC Educational Resources Information Center

    Rowland, Melisa D.; Chapman, Jason E.; Henggeler, Scott W.

    2008-01-01

    This study examined the substance use and delinquency outcomes for the nearest age siblings of substance abusing and delinquent adolescents that participated in a randomized clinical trial evaluating the effectiveness of integrating evidence-based practices into juvenile drug court. The sample of 70 siblings averaged 14.4 years of age, 50% were…

  7. Site Matters: Multisite Randomized Trial of Motivational Enhancement Therapy in Community Drug Abuse Clinics

    ERIC Educational Resources Information Center

    Ball, Samuel A.; Martino, Steve; Nich, Charla; Frankforter, Tami L.; Van Horn, Deborah; Crits-Christoph, Paul; Woody, George E.; Obert, Jeanne L.; Farentinos, Christiane; Carroll, Kathleen M.

    2007-01-01

    The effectiveness of motivational enhancement therapy (MET) in comparison with counseling as usual (CAU) for increasing retention and reducing substance use was evaluated in a multisite randomized clinical trial. Participants were 461 outpatients treated by 31 therapists within 1 of 5 outpatient substance abuse programs. There were no retention…

  8. A Randomized Trial of Wraparound Facilitation versus Usual Child Protection Services

    ERIC Educational Resources Information Center

    Browne, Dillon T.; Puente-Duran, Sofia; Shlonsky, Aron; Thabane, Lehana; Verticchio, Dominic

    2016-01-01

    Objective: To evaluate whether the addition of a wraparound facilitator to regular child protection services improved child and family functioning over 20 months. Method: A single blind randomized controlled trial with concealment and stratification across three sites (N = 135 eligible families with substantiated maltreatment). Results: Based on 2…

  9. Statistical Analysis for Multisite Trials Using Instrumental Variables with Random Coefficients

    ERIC Educational Resources Information Center

    Raudenbush, Stephen W.; Reardon, Sean F.; Nomi, Takako

    2012-01-01

    Multisite trials can clarify the average impact of a new program and the heterogeneity of impacts across sites. Unfortunately, in many applications, compliance with treatment assignment is imperfect. For these applications, we propose an instrumental variable (IV) model with person-specific and site-specific random coefficients. Site-specific IV…

  10. Cancer Screening Knowledge Changes: Results from a Randomized Control Trial of Women with Developmental Disabilities

    ERIC Educational Resources Information Center

    Parish, Susan L.; Rose, Roderick A.; Luken, Karen; Swaine, Jamie G.; O'Hare, Lindsey

    2012-01-01

    Background: Women with developmental disabilities are much less likely than nondisabled women to receive cervical and breast cancer screening according to clinical guidelines. One barrier to receipt of screenings is a lack of knowledge about preventive screenings. Method: To address this barrier, we used a randomized control trial (n = 175 women)…

  11. Factors Influencing Hand Washing Behaviour in Primary Schools: Process Evaluation within a Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Chittleborough, Catherine R.; Nicholson, Alexandra L.; Basker, Elaine; Bell, Sarah; Campbell, Rona

    2012-01-01

    This article explores factors that may influence hand washing behaviour among pupils and staff in primary schools. A qualitative process evaluation within a cluster randomized controlled trial included pupil focus groups (n = 16, aged 6-11 years), semi-structured interviews (n = 16 teachers) and observations of hand washing facilities (n = 57).…

  12. Randomized Control Trial of a CBT Trauma Recovery Program in Palestinian Schools

    ERIC Educational Resources Information Center

    Barron, Ian G.; Abdallah, Ghassan; Smith, Patrick

    2013-01-01

    The current study aimed to assess the Teaching Recovery Techniques (TRT) trauma recovery program within the context of ongoing violence. Utilizing a randomized controlled trial, 11-14-year-old students in Nablus, Palestine, were allocated by class to intervention or wait-list control conditions. Standardized measures assessed trauma exposure,…

  13. Fit 5 Kids TV reduction program for Latino preschoolers: A cluster randomized controlled trial

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reducing Latino preschoolers' TV viewing is needed to reduce their risk of obesity and other chronic diseases. This study's objective was to evaluate the Fit 5 Kids (F5K) TV reduction program's impact on Latino preschooler's TV viewing. The study design was a cluster randomized controlled trial (RCT...

  14. Randomized Controlled Trial: Multimodal Anxiety and Social Skill Intervention for Adolescents with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    White, Susan W.; Ollendick, Thomas; Albano, Anne Marie; Oswald, Donald; Johnson, Cynthia; Southam-Gerow, Michael A.; Kim, Inyoung; Scahill, Lawrence

    2013-01-01

    Anxiety is common among adolescents with autism spectrum disorders (ASD) and may amplify the core social disability, thus necessitating combined treatment approaches. This pilot, randomized controlled trial evaluated the feasibility and preliminary outcomes of the Multimodal Anxiety and Social Skills Intervention (MASSI) program in a sample of 30…

  15. A Randomized Controlled Trial of Hanen's "More than Words" in Toddlers with Early Autism Symptoms

    ERIC Educational Resources Information Center

    Carter, Alice S.; Messinger, Daniel S.; Stone, Wendy L.; Celimli, Seniz; Nahmias, Allison S.; Yoder, Paul

    2011-01-01

    Background: This randomized controlled trial compared Hanen's "More than Words" (HMTW), a parent-implemented intervention, to a "business as usual" control group. Methods: Sixty-two children (51 boys and 11 girls; M age = 20 months; SD = 2.6) who met criteria for autism spectrum disorders (ASD) and their parents participated in the study. The HMTW…

  16. Escitalopram in the Treatment of Adolescent Depression: A Randomized Placebo-Controlled Multisite Trial

    ERIC Educational Resources Information Center

    Emslie, Graham J.; Ventura, Daniel; Korotzer, Andrew; Tourkodimitris, Stavros

    2009-01-01

    A randomized, double-blind, placebo-controlled trial that involves 312 male and female patients aged 12-17 reveal the effectiveness of escitalopram in the treatment of depressed adolescents. Eighty-three percent of the participants or 259 participants completed the 8 weeks therapy period.

  17. Randomized trial of exclusive human milk versus preterm formula diets in extremely premature infants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our objective was to compare the duration of parenteral nutrition, growth, and morbidity in extremely premature infants fed exclusive diets of either bovine milk-based preterm formula (BOV) or donor human milk and human milk-based human milk fortifier (HUM), in a randomized trial of formula vs human...

  18. Brief Treatments for Cannabis Dependence: Findings From a Randomized Multisite Trial

    ERIC Educational Resources Information Center

    Babor, Thomas F.

    2004-01-01

    This study evaluated the efficacy of 2 brief interventions for cannabis-dependent adults. A multisite randomized controlled trial compared cannabis use outcomes across 3 study conditions: (a) 2 sessions of motivational enhancement therapy (MET); (b) 9 sessions of multicomponent therapy that included MET, cognitive-behavioral therapy, and case…

  19. Randomized Trial of Internet-Delivered Self-Help with Telephone Support for Pathological Gamblers

    ERIC Educational Resources Information Center

    Carlbring, Per; Smit, Filip

    2008-01-01

    Although effective therapies for pathological gambling exist, their uptake is limited to 10% of the target population. To lower the barriers for help seeking, the authors tested an online alternative in a randomized trial (N = 66). The participants were pathological gamblers not presenting with severe comorbid depression. A wait-list control was…

  20. Randomized Trials on Consider This, a Tailored, Internet-Delivered Smoking Prevention Program for Adolescents

    ERIC Educational Resources Information Center

    Buller, David B.; Borland, Ron; Woodall, W. Gill; Hall, John R.; Hines, Joan M.; Burris-Woodall, Patricia; Cutter, Gary R.; Miller, Caroline; Balmford, James; Starling, Randall; Ax, Bryan; Saba, Laura

    2008-01-01

    The Internet may be an effective medium for delivering smoking prevention to children. Consider This, an Internet-based program, was hypothesized to reduce expectations concerning smoking and smoking prevalence. Group-randomized pretest-posttest controlled trials were conducted in Australia (n = 2,077) and the United States (n = 1,234) in schools…

  1. Mindfulness-Based Stress Reduction for the Treatment of Adolescent Psychiatric Outpatients: A Randomized Clinical Trial

    ERIC Educational Resources Information Center

    Biegel, Gina M.; Brown, Kirk Warren; Shapiro, Shauna L.; Schubert, Christine M.

    2009-01-01

    Research has shown that mindfulness-based treatment interventions may be effective for a range of mental and physical health disorders in adult populations, but little is known about the effectiveness of such interventions for treating adolescent conditions. The present randomized clinical trial was designed to assess the effect of the…

  2. A Randomized Effectiveness Trial of Brief Parent Training: Six-Month Follow-Up

    ERIC Educational Resources Information Center

    Kjøbli, John; Bjørnebekk, Gunnar

    2013-01-01

    Objective: To examine the follow-up effectiveness of brief parent training (BPT) for children with emerging or existing conduct problems. Method: With the use of a randomized controlled trial and parent and teacher reports, this study examined the effectiveness of BPT compared to regular services 6 months after the end of the intervention.…

  3. Dissonance and Healthy Weight Eating Disorder Prevention Programs: A Randomized Efficacy Trial

    ERIC Educational Resources Information Center

    Stice, Eric; Shaw, Heather; Burton, Emily; Wade, Emily

    2006-01-01

    In this trial, adolescent girls with body dissatisfaction (N = 481, M age = 17 years) were randomized to an eating disorder prevention program involving dissonance-inducing activities that reduce thin-ideal internalization, a prevention program promoting healthy weight management, an expressive writing control condition, or an assessment-only…

  4. Why Randomized Trials Are Challenging within Adventure Therapy Research: Lessons Learned in Norway

    ERIC Educational Resources Information Center

    Gabrielsen, Leiv Einar; Fernee, Carina Ribe; Aasen, Gunnar Oland; Eskedal, Leif Torvald

    2016-01-01

    There are few high-quality studies using randomized controlled trials (RCTs) in the adventure and wilderness therapy literature. Thus, a unison call is heard for more such studies to be carried out. This article presents a Norwegian wilderness therapy research project that planned to incorporate this "gold standard" that is regarded as…

  5. An Intervention for Sensory Difficulties in Children with Autism: A Randomized Trial

    ERIC Educational Resources Information Center

    Schaaf, Roseann C.; Benevides, Teal; Mailloux, Zoe; Faller, Patricia; Hunt, Joanne; van Hooydonk, Elke; Freeman, Regina; Leiby, Benjamin; Sendecki, Jocelyn; Kelly, Donna

    2014-01-01

    This study evaluated a manualized intervention for sensory difficulties for children with autism, ages 4-8 years, using a randomized trial design. Diagnosis of autism was confirmed using gold standard measures. Results show that the children in the treatment group (n = 17) who received 30 sessions of the occupational therapy intervention scored…

  6. Randomized Controlled Trial of Video Self-Modeling Following Speech Restructuring Treatment for Stuttering

    ERIC Educational Resources Information Center

    Cream, Angela; O'Brian, Sue; Jones, Mark; Block, Susan; Harrison, Elisabeth; Lincoln, Michelle; Hewat, Sally; Packman, Ann; Menzies, Ross; Onslow, Mark

    2010-01-01

    Purpose: In this study, the authors investigated the efficacy of video self-modeling (VSM) following speech restructuring treatment to improve the maintenance of treatment effects. Method: The design was an open-plan, parallel-group, randomized controlled trial. Participants were 89 adults and adolescents who undertook intensive speech…

  7. Cycling Versus Continuous Mode In Neuromodulator Programming: A Crossover, Randomized, Controlled Trial.

    PubMed

    Beer, Gwendolyn M; Gurule, Margaret M; Komesu, Yuko M; Qualls, Clifford R; Rogers, Rebecca G

    2016-01-01

    This is a randomized, controlled, blind, crossover trial comparing cycling versus continuous programming of a sacral neuromodulator in women diagnosed with overactive bladder (OAB). At 6 months, treatment order significantly affected Overactive Bladder Questionnaire - Short Form (OABq-SF) symptom scores. The cycling followed by continuous stimulation group had superior OABq-SF scores (p > 0.02). PMID:27501593

  8. Mainstreaming Remedial Mathematics Students in Introductory Statistics: Results Using a Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Logue, Alexandra W.; Watanabe-Rose, Mari

    2014-01-01

    This study used a randomized controlled trial to determine whether students, assessed by their community colleges as needing an elementary algebra (remedial) mathematics course, could instead succeed at least as well in a college-level, credit-bearing introductory statistics course with extra support (a weekly workshop). Researchers randomly…

  9. Effects of Assertiveness Training and Expressive Writing on Acculturative Stress in International Students: A Randomized Trial

    ERIC Educational Resources Information Center

    Tavakoli, Shedeh; Lumley, Mark A.; Hijazi, Alaa M.; Slavin-Spenny, Olga M.; Parris, George P.

    2009-01-01

    International university students often experience acculturative stress, and culturally appropriate techniques to manage stress are needed. This randomized trial tested the effects of group assertiveness training, private expressive writing, their combination, and a wait-list control on the acculturative stress, affect, and health of 118…

  10. A Compound Herbal Preparation (CHP) in the Treatment of Children with ADHD: A Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Katz, M.; Adar Levine, A.; Kol-Degani, H.; Kav-Venaki, L.

    2010-01-01

    Objective: Evaluation of the efficacy of a patented, compound herbal preparation (CHP) in improving attention, cognition, and impulse control in children with ADHD. Method: Design: A randomized, double-blind, placebo-controlled trial. Setting: University-affiliated tertiary medical center. Participants: 120 children newly diagnosed with ADHD,…

  11. Attachment-Based Family Therapy for Adolescents with Suicidal Ideation: A Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Diamond, Guy S.; Wintersteen, Matthew B.; Brown, Gregory K.; Diamond, Gary M.; Gallop, Robert; Shelef, Karni; Levy, Suzanne

    2010-01-01

    Objective: To evaluate whether Attachment-Based Family Therapy (ABFT) is more effective than Enhanced Usual Care (EUC) for reducing suicidal ideation and depressive symptoms in adolescents. Method: This was a randomized controlled trial of suicidal adolescents between the ages of 12 and 17, identified in primary care and emergency departments. Of…

  12. Randomized Controlled Non-Inferiority Trial of a Telehealth Treatment for Chronic Stuttering: The Camperdown Program

    ERIC Educational Resources Information Center

    Carey, Brenda; O'Brian, Sue; Onslow, Mark; Block, Susan; Jones, Mark; Packman, Ann

    2010-01-01

    Background: Although there are treatments that can alleviate stuttering in adults for clinically significant periods, in Australia there are barriers to the accessibility and availability of best-practice treatment. Aims: This parallel group, non-inferiority randomized controlled trial with multiple blinded outcome assessments investigated whether…

  13. Early Development of Delinquency within Divorced Families: Evaluating a Randomized Preventive Intervention Trial

    ERIC Educational Resources Information Center

    DeGarmo, David S.; Forgatch, Marion S.

    2005-01-01

    This paper reports on an experimental test of coercion theory early onset model of delinquency. Results are from the Oregon Divorce Study-II, a randomized preventive intervention trial with a sample of 238 recently separated mothers and their sons in early elementary school. The objective was to experimentally manipulate parenting variables…

  14. Educational Effects of the Tools of the Mind Curriculum: A Randomized Trial

    ERIC Educational Resources Information Center

    Barnett, W.Steven; Jung, Kwanghee; Yarosz, Donald J.; Thomas, Jessica; Hornbeck, Amy; Stechuk, Robert; Burns, Susan

    2008-01-01

    The effectiveness of the "Tools of the Mind (Tools)" curriculum in improving the education of 3- and 4-year-old children was evaluated by means of a randomized trial. The "Tools" curriculum, based on the work of Vygotsky, focuses on the development of self-regulation at the same time as teaching literacy and mathematics skills in a way that is…

  15. Positive Family Intervention for Severe Challenging Behavior I: A Multisite Randomized Clinical Trial

    ERIC Educational Resources Information Center

    Durand, V. Mark; Hieneman, Meme; Clarke, Shelley; Wang, Mo; Rinaldi, Melissa L.

    2013-01-01

    The present study was a multisite randomized clinical trial assessing the effects of adding a cognitive-behavioral intervention to positive behavior support (PBS). Fifty-four families who met the criteria of (a) having a child with a developmental disability, (b) whose child displayed serious challenging behavior (e.g., aggression, self-injury,…

  16. A Randomized Clinical Trial of Alternative Stress Management Interventions in Persons with HIV Infection

    ERIC Educational Resources Information Center

    McCain, Nancy L.; Gray, D. Patricia; Elswick, R. K., Jr.; Robins, Jolynne W.; Tuck, Inez; Walter, Jeanne M.; Rausch, Sarah M.; Ketchum, Jessica McKinney

    2008-01-01

    Research in psychoneuroimmunology suggests that immunosuppression associated with perceived stress may contribute to disease progression in persons with HIV infection. While stress management interventions may enhance immune function, few alternative approaches have yet been tested. This randomized clinical trial was conducted to test effects of…

  17. Competitive Employment for Youth with Autism Spectrum Disorders: Early Results from a Randomized Clinical Trial

    ERIC Educational Resources Information Center

    Wehman, Paul H.; Schall, Carol M.; McDonough, Jennifer; Kregel, John; Brooke, Valerie; Molinelli, Alissa; Ham, Whitney; Graham, Carolyn W.; Riehle, J. Erin; Collins, Holly T.; Thiss, Weston

    2014-01-01

    For most youth with autism spectrum disorders (ASD), employment upon graduation from high school or college is elusive. Employment rates are reported in many studies to be very low despite many years of intensive special education services. This paper presented the preliminary results of a randomized clinical trial of Project SEARCH plus ASD…

  18. Enhancing Attachment Organization among Maltreated Children: Results of a Randomized Clinical Trial

    ERIC Educational Resources Information Center

    Bernard, Kristin; Dozier, Mary; Bick, Johanna; Lewis-Morrarty, Erin; Lindhiem, Oliver; Carlson, Elizabeth

    2012-01-01

    Young children who have experienced early adversity are at risk for developing disorganized attachments. The efficacy of Attachment and Biobehavioral Catch-up (ABC), an intervention targeting nurturing care among parents identified as being at risk for neglecting their young children, was evaluated through a randomized clinical trial. Attachment…

  19. Monthly high dose vitamin D treatment for the prevention of functional decline: a randomized clinical trial

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Importance: Vitamin D deficiency has been associated with poor physical performance. Objective: To determine the effectiveness of high dose vitamin D in lowering the risk of functional decline. Design, Setting, and Participants: One-year double-blind, randomized clinical trial conducted in Zurich,...

  20. Cognitive-Behavioral Therapy for Intermittent Explosive Disorder: A Pilot Randomized Clinical Trial

    ERIC Educational Resources Information Center

    McCloskey, Michael S.; Noblett, Kurtis L.; Deffenbacher, Jerry L.; Gollan, Jackie K.; Coccaro, Emil F.

    2008-01-01

    No randomized clinical trials have evaluated the efficacy of psychotherapy for intermittent explosive disorder (IED). In the present study, the authors tested the efficacy of 12-week group and individual cognitive-behavioral therapies (adapted from J. L. Deffenbacher & M. McKay, 2000) by comparing them with a wait-list control in a randomized…

  1. Acupuncture for Children with Autism Spectrum Disorders: A Systematic Review of Randomized Clinical Trials

    ERIC Educational Resources Information Center

    Lee, Myeong Soo; Choi, Tae-Young; Shin, Byung-Cheul; Ernst, Edzard

    2012-01-01

    This study aimed to assess the effectiveness of acupuncture as a treatment for autism spectrum disorders (ASD). We searched the literature using 15 databases. Eleven randomized clinical trials (RCTs) met our inclusion criteria. Most had significant methodological weaknesses. The studies' statistical and clinical heterogeneity prevented us from…

  2. Effect of Improving the Usability of an E-Learning Resource: A Randomized Trial

    ERIC Educational Resources Information Center

    Davids, Mogamat Razeen; Chikte, Usuf M. E.; Halperin, Mitchell L.

    2014-01-01

    Optimizing the usability of e-learning materials is necessary to reduce extraneous cognitive load and maximize their potential educational impact. However, this is often neglected, especially when time and other resources are limited. We conducted a randomized trial to investigate whether a usability evaluation of our multimedia e-learning…

  3. Financial Incentives and Student Achievement: Evidence from Randomized Trials. NBER Working Paper No. 15898

    ERIC Educational Resources Information Center

    Fryer, Roland G., Jr.

    2010-01-01

    This paper describes a series of school-based randomized trials in over 250 urban schools designed to test the impact of financial incentives on student achievement. In stark contrast to simple economic models, our results suggest that student incentives increase achievement when the rewards are given for inputs to the educational production…

  4. A Pilot Randomized Controlled Trial of Omega-3 Fatty Acids for Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Bent, Stephen; Bertoglio, Kiah; Ashwood, Paul; Bostrom, Alan; Hendren, Robert L.

    2011-01-01

    We conducted a pilot randomized controlled trial to determine the feasibility and initial safety and efficacy of omega-3 fatty acids (1.3 g/day) for the treatment of hyperactivity in 27 children ages 3-8 with autism spectrum disorder (ASD). After 12 weeks, hyperactivity, as measured by the Aberrant Behavior Checklist, improved 2.7 (plus or minus…

  5. The Effectiveness of Healthy Start Home Visit Program: Cluster Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Leung, Cynthia; Tsang, Sandra; Heung, Kitty

    2015-01-01

    Purpose: The study reported the effectiveness of a home visit program for disadvantaged Chinese parents with preschool children, using cluster randomized controlled trial design. Method: Participants included 191 parents and their children from 24 preschools, with 84 dyads (12 preschools) in the intervention group and 107 dyads (12 preschools) in…

  6. Learning What Works in ITS from Non-Traditional Randomized Controlled Trial Data

    ERIC Educational Resources Information Center

    Pardos, Zachary A.; Dailey, Matthew D.; Heffernan, Neil T.

    2011-01-01

    The well established, gold standard approach to finding out what works in education research is to run a randomized controlled trial (RCT) using a standard pre-test and post-test design. RCTs have been used in the intelligent tutoring community for decades to determine which questions and tutorial feedback work best. Practically speaking, however,…

  7. Using Multilevel Mixtures to Evaluate Intervention Effects in Group Randomized Trials

    ERIC Educational Resources Information Center

    Van Horn, M. Lee; Fagan, Abigail A.; Jaki, Thomas; Brown, Eric C.; Hawkins, J. David; Arthur, Michael W.; Abbott, Robert D.; Catalano, Richard F.

    2008-01-01

    There is evidence to suggest that the effects of behavioral interventions may be limited to specific types of individuals, but methods for evaluating such outcomes have not been fully developed. This study proposes the use of finite mixture models to evaluate whether interventions, and, specifically, group randomized trials, impact participants…

  8. Benefits and Harms of Sick Leave: Lack of Randomized, Controlled Trials

    ERIC Educational Resources Information Center

    Axelsson, Inge; Marnetoft, Sven-Uno

    2010-01-01

    The aim of this study was to try to identify those randomized controlled trials that compare sick leave with no sick leave or a different duration or degree of sick leave. A comprehensive, systematic, electronic search of Clinical Evidence, the Cochrane Library and PubMed, and a manual search of the Campbell Library and a journal supplement was…

  9. A Randomized Trial of a Multifaceted Intervention to Reduce Falls among Community-Dwelling Adults

    ERIC Educational Resources Information Center

    Fox, Patrick J.; Vazquez, Laurie; Tonner, Chris; Stevens, Judy A.; Fineman, Norman; Ross, Leslie K.

    2010-01-01

    Using a randomized controlled trial, we tested the efficacy of a fall prevention intervention to reduce falls among adults in a community-based health promotion program. Adults aged 65 and older within two counties were recruited (control n = 257; intervention n = 286). After 12 months, there was a significant decrease in the number of falls in…

  10. Sample Size Estimation in Cluster Randomized Educational Trials: An Empirical Bayes Approach

    ERIC Educational Resources Information Center

    Rotondi, Michael A.; Donner, Allan

    2009-01-01

    The educational field has now accumulated an extensive literature reporting on values of the intraclass correlation coefficient, a parameter essential to determining the required size of a planned cluster randomized trial. We propose here a simple simulation-based approach including all relevant information that can facilitate this task. An…

  11. Encouraging the Flight of Error: Ethical Standards, Evidence Standards, and Randomized Trials

    ERIC Educational Resources Information Center

    Boruch, Robert

    2007-01-01

    Thomas Jefferson recognized the value of reason and scientific experimentation in the eighteenth century. This chapter extends the idea in contemporary ways to standards that may be used to judge the ethical propriety of randomized trials and the dependability of evidence on effects of social interventions.

  12. A Randomized Effectiveness Trial of Brief Cognitive-Behavioral Therapy for Depressed Adolescents Receiving Antidepressant Medication

    ERIC Educational Resources Information Center

    Clarke, Gregory; DeBar, Lynn; Lynch, Frances; Powell, James; Gale, John; O'Connor, Elizabeth; Ludman, Evette; Bush, Terry; Lin, Elizabeth H. B.; Von Korff, Michael; Hertert, Stephanie

    2005-01-01

    Objective: To test a collaborative-care, cognitive-behavioral therapy (CBT) program adjunctive to selective serotonin reuptake inhibitor (SSRI) treatment in HMO pediatric primary care. Method: A randomized effectiveness trial comparing a treatment-as-usual (TAU) control condition consisting primarily of SSRI medication delivered outside the…

  13. Can Babies Learn to Read? A Randomized Trial of Baby Media

    ERIC Educational Resources Information Center

    Neuman, Susan B.; Kaefer, Tanya; Pinkham, Ashley; Strouse, Gabrielle

    2014-01-01

    Targeted to children as young as 3 months old, there is a growing number of baby media products that claim to teach babies to read. This randomized controlled trial was designed to examine this claim by investigating the effects of a best-selling baby media product on reading development. One hundred and seventeen infants, ages 9 to 18 months,…

  14. Installing the Communities that Care Prevention System: Implementation Progress and Fidelity in a Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Quinby, Rose K.; Hanson, Koren; Brooke-Weiss, Blair; Arthur, Michael W.; Hawkins, J. David; Fagan, Abigail A.

    2008-01-01

    This article describes the degree to which high fidelity implementation of the Communities That Care (CTC) prevention operating system was reached during the first 18 months of intervention in 12 communities in the Community Youth Development Study, a 5-year group randomized controlled trial designed to test the efficacy of the CTC system. CTC…

  15. Randomized Controlled Trial of the Focus Parent Training for Toddlers with Autism: 1-Year Outcome

    ERIC Educational Resources Information Center

    Oosterling, Iris; Visser, Janne; Swinkels, Sophie; Rommelse, Nanda; Donders, Rogier; Woudenberg, Tim; Roos, Sascha; van der Gaag, Rutger Jan; Buitelaar, Jan

    2010-01-01

    This randomized controlled trial compared results obtained after 12 months of nonintensive parent training plus care-as-usual and care-as-usual alone. The training focused on stimulating joint attention and language skills and was based on the intervention described by Drew et al. (Eur Child Adolesc Psychiatr 11:266-272, 2002). Seventy-five…

  16. Parent Training for Young Children with Developmental Disabilities: Randomized Controlled Trial

    ERIC Educational Resources Information Center

    McIntyre, Laura Lee

    2008-01-01

    A randomized controlled trial was used to evaluate a parent training intervention for caregivers with preschool-age children with developmental disabilities. The 21 families in the experimental group received usual care plus the 12-week Incredible Years Parent Training Program with developmental delay modifications. Families in the control group…

  17. Computerized Training of Working Memory in Children with ADHD-A Randomized, Controlled Trial

    ERIC Educational Resources Information Center

    Klingberg, Torkel; Fernell, Elisabeth; Olesen, Pernille J.; Johnson, Mats; Gustafsson, Per; Dahlstrom, Kerstin; Gillberg, Christopher G.; Forssberg, Hans; Westerberg, Helena

    2005-01-01

    Objective: Deficits in executive functioning, including working memory (WM) deficits, have been suggested to be important in attention-deficit/hyperactivity disorder (ADHD). During 2002 to 2003, the authors conducted a multicenter, randomized, controlled, double-blind trial to investigate the effect of improving WM by computerized, systematic…

  18. Aquatic Physical Therapy for Children with Developmental Coordination Disorder: A Pilot Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Hillier, Susan; McIntyre, Auburn; Plummer, Leanne

    2010-01-01

    Aquatic therapy is an intervention for children with Developmental Coordination Disorder (DCD) that has not been investigated formally. This was a pilot randomized controlled trial to investigate the feasibility and preliminary effectiveness of an aquatic therapy program to improve motor skills of children with DCD. Thirteen children (mean age 7…

  19. The Efficiency and Efficacy of Equivalence-Based Learning: A Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Zinn, Tracy E.; Newland, M. Christopher; Ritchie, Katie E.

    2015-01-01

    Because it employs an emergent-learning framework, equivalence-based instruction (EBI) is said to be highly efficient, but its presumed benefits must be compared quantitatively with alternative techniques. In a randomized controlled trial, 61 college students attempted to learn 32 pairs of proprietary and generic drug names using computer-based…

  20. Randomized, Controlled Trial to Examine the Impact of Providing Yogurt to Women Enrolled in WIC

    ERIC Educational Resources Information Center

    Fung, Ellen B.; Ritchie, Lorrene D.; Walker, Brent H.; Gildengorin, Ginny; Crawford, Patricia B.

    2010-01-01

    Objective: Examine the impact of providing yogurt to women enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). Design: Randomized, controlled intervention trial. Setting: Two California WIC local agency sites. Participants: 511 pregnant, breast-feeding, or postpartum women. Intervention: Substitution of…

  1. Effectiveness of a Parent Training Program in (Pre)Adolescence: Evidence from a Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Leijten, Patty; Overbeek, Geertjan; Janssens, Jan M. A. M.

    2012-01-01

    The present randomized controlled trial examined the effectiveness of the parent training program Parents and Children Talking Together (PCTT) for parents with children in the preadolescent period who experience parenting difficulties. The program is focused on reducing child problem behavior by improving parents' communication and problem solving…

  2. Treatment Preferences Affect the Therapeutic Alliance: Implications for Randomized Controlled Trials

    ERIC Educational Resources Information Center

    Iacoviello, Brian M.; McCarthy, Kevin Scott; Barrett, Marna S.; Rynn, Moira; Gallop, Robert; Barber, Jacques P.

    2007-01-01

    The influence of treatment preferences on the development of the therapeutic alliance was investigated. Seventy-five patients were followed while participating in a randomized controlled trial comparing supportive-expressive psychotherapy with sertraline or pill placebo in the treatment of major depressive disorder. Therapeutic alliance was…

  3. Sustainability of the Dissemination of an Occupational Sun Protection Program in a Randomized Trial

    ERIC Educational Resources Information Center

    Buller, David B.; Walkosz, Barbara J.; Andersen, Peter A.; Scott, Michael D.; Dignan, Mark B.; Cutter, Gary R.; Zhang, Xiao; Kane, Ilima L.

    2012-01-01

    Sustainability of an occupational sun safety program, Go Sun Smart (GSS), was explored in a randomized trial, testing dissemination strategies at 68 U.S. and Canadian ski areas in 2004-2007. All ski areas received GSS from the National Ski Areas Association through a Basic Dissemination Strategy (BDS) using conference presentations and free…

  4. Randomized Trial of Anger Control Training for Adolescents with Tourette's Syndrome and Disruptive Behavior

    ERIC Educational Resources Information Center

    Sukhdolsky, Denis G.; Vitulano, Lawrence A.; Carroll, Deirdre H.; McGuire, Joseph; Leckman, James F.; Scahill, Lawrence

    2009-01-01

    A randomized trial to examine the efficacy of anger control training for treating adolescents with Tourette's syndrome and disruptive behavior reveals that those administered with the anger control training showed a decrease in their Disruptive Behavior Rating Scale score by 52 percent as compared with a decrease of 11 percent in the treatment as…

  5. Moving from Efficacy to Effectiveness in Cognitive Behavioral Therapy for Psychosis: A Randomized Clinical Practice Trial

    ERIC Educational Resources Information Center

    Lincoln, Tania M.; Ziegler, Michael; Mehl, Stephanie; Kesting, Marie-Luise; Lullmann, Eva; Westermann, Stefan; Rief, Winfried

    2012-01-01

    Objective: Randomized controlled trials have attested the efficacy of cognitive behavioral therapy (CBT) in reducing psychotic symptoms. Now, studies are needed to investigate its effectiveness in routine clinical practice settings. Method: Eighty patients with schizophrenia spectrum disorders who were seeking outpatient treatment were randomized…

  6. Treatment of Co-Occurring Substance Abuse and Suicidality among Adolescents: A Randomized Trial

    ERIC Educational Resources Information Center

    Esposito-Smythers, Christianne; Spirito, Anthony; Kahler, Christopher W.; Hunt, Jeffrey; Monti, Peter

    2011-01-01

    Objective: This study tested a cognitive-behavioral treatment protocol for adolescents with a co-occurring alcohol or other drug use disorder (AOD) and suicidality in a randomized clinical trial. Method: Forty adolescents (M[subscript age] = 15 years; 68% female, 89% White) and their families recruited from an inpatient psychiatric hospital were…

  7. Methylprednisolone in the management of spinal cord injuries: Lessons from randomized, controlled trials

    PubMed Central

    Cheung, Vincent; Hoshide, Reid; Bansal, Vishal; Kasper, Ekkehard; Chen, Clark C.

    2015-01-01

    The efficacy of glucocorticoid for treatment of acute spinal cord injuries remains a controversial topic. Differing medical societies have issued conflicting recommendations in this regard. Here we review the available randomized, controlled trial (RCT) data on this subject and offer a synthesis of these data sets. PMID:26392918

  8. Group Lidcombe Program Treatment for Early Stuttering: A Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Arnott, Simone; Onslow, Mark; O'Brian, Sue; Packman, Ann; Jones, Mark; Block, Susan

    2014-01-01

    Purpose: This study adds to the Lidcombe Program evidence base by comparing individual and group treatment of preschoolers who stutter. Method: A randomized controlled trial of 54 preschoolers was designed to establish whether group delivery outcomes were not inferior to the individual model. The group arm used a rolling group model, in which a…

  9. A Randomized Trial of a Multimodal Community-Based Prisoner Reentry Program Emphasizing Substance Abuse Treatment

    ERIC Educational Resources Information Center

    Grommon, Eric; Davidson, William S., II; Bynum, Timothy S.

    2013-01-01

    Prisoner reentry programs continue to be developed and implemented to ease the process of transition into the community and to curtail fiscal pressures. This study describes and provides relapse and recidivism outcome findings related to a randomized trial evaluating a multimodal, community-based reentry program that prioritized substance abuse…

  10. A Randomized Controlled Trial of a Behavioral Economic Supplement to Brief Motivational Interventions for College Drinking

    ERIC Educational Resources Information Center

    Murphy, James G.; Dennhardt, Ashley A.; Skidmore, Jessica R.; Borsari, Brian; Barnett, Nancy P.; Colby, Suzanne M.; Martens, Matthew P.

    2012-01-01

    Objective: Behavioral economic theory suggests that a reduction in substance use is most likely when there is an increase in rewarding substance-free activities. The goal of this randomized controlled clinical trial was to evaluate the incremental efficacy of a novel behavioral economic supplement (Substance-Free Activity Session [SFAS]) to a…

  11. A Randomized Controlled Trial Study of the ABRACADABRA Reading Intervention Program in Grade 1

    ERIC Educational Resources Information Center

    Savage, Robert S.; Abrami, Philip; Hipps, Geoffrey; Deault, Louise

    2009-01-01

    This study reports a randomized controlled trial evaluation of a computer-based balanced literacy intervention, ABRACADABRA (http://grover.concordia.ca/abra/version1/abracadabra.html). Children (N = 144) in Grade 1 were exposed either to computer activities for word analysis, text comprehension, and fluency, alongside shared stories (experimental…

  12. Reconsidering Findings of "No Effects" in Randomized Control Trials: Modeling Differences in Treatment Impacts

    ERIC Educational Resources Information Center

    Chaney, Bradford

    2016-01-01

    The primary technique that many researchers use to analyze data from randomized control trials (RCTs)--detecting the average treatment effect (ATE)--imposes assumptions upon the data that often are not correct. Both theory and past research suggest that treatments may have significant impacts on subgroups even when showing no overall effect.…

  13. A Randomized Trial of Probation Case Management for Drug-Involved Women Offenders

    ERIC Educational Resources Information Center

    Guydish, Joseph; Chan, Monica; Bostrom, Alan; Jessup, Martha A.; Davis, Thomas B.; Marsh, Cheryl

    2011-01-01

    This article reports findings from a clinical trial of a probation case management (PCM) intervention for drug-involved women offenders. Participants were randomly assigned to PCM (n = 92) or standard probation (n = 91) and followed for 12 months using measures of substance abuse, psychiatric symptoms, social support, and service utilization.…

  14. Using Small-Scale Randomized Controlled Trials to Evaluate the Efficacy of New Curricular Materials

    ERIC Educational Resources Information Center

    Drits-Esser, Dina; Bass, Kristin M.; Stark, Louisa A.

    2014-01-01

    How can researchers in K-12 contexts stay true to the principles of rigorous evaluation designs within the constraints of classroom settings and limited funding? This paper explores this question by presenting a small-scale randomized controlled trial (RCT) designed to test the efficacy of curricular supplemental materials on epigenetics. The…

  15. The Effectiveness of Two Grammar Treatment Procedures for Children with SLI: A Randomized Clinical Trial

    ERIC Educational Resources Information Center

    Smith-Lock, Karen M.; Leitão, Suze; Prior, Polly; Nickels, Lyndsey

    2015-01-01

    Purpose: This study compared the effectiveness of two grammar treatment procedures for children with specific language impairment. Method: A double-blind superiority trial with cluster randomization was used to compare a cueing procedure, designed to elicit a correct production following an initial error, to a recasting procedure, which required…

  16. Randomized Trial of a Broad Preventive Intervention for Mexican American Adolescents

    ERIC Educational Resources Information Center

    Gonzales, Nancy A.; Dumka, Larry E.; Millsap, Roger E.; Gottschall, Amanda; McClain, Darya B.; Wong, Jessie J.; German, Miguelina; Mauricio, Anne M.; Wheeler, Lorey; Carpentier, Francesca D.; Kim, Su Yeong

    2012-01-01

    Objective: This randomized trial of a family-focused preventive intervention for Mexican American (MA) adolescents evaluated intervention effects on adolescent substance use, internalizing and externalizing symptoms, and school discipline and grade records in 8th grade, 1 year after completion of the intervention. The study also examined…

  17. Randomized Trial Comparison of Emotion Regulation and Relational Psychotherapies for PTSD with Girls Involved in Delinquency

    ERIC Educational Resources Information Center

    Ford, Julian D.; Steinberg, Karen L.; Hawke, Josephine; Levine, Joan; Zhang, Wanli

    2012-01-01

    Posttraumatic stress disorder (PTSD) is prevalent in youth involved in delinquency, but it is often not effectively treated. A randomized clinical trial was conducted comparing the outcomes of an emotion regulation therapy (Trauma Affect Regulation: Guide for Education and Therapy, or TARGET) with a relational supportive therapy (Enhanced…

  18. Computer-Assisted Learning in Elementary Reading: A Randomized Control Trial

    ERIC Educational Resources Information Center

    Shannon, Lisa Cassidy; Styers, Mary Koenig; Wilkerson, Stephanie Baird; Peery, Elizabeth

    2015-01-01

    This study evaluated the efficacy of Accelerated Reader, a computer-based learning program, at improving student reading. Accelerated Reader is a progress-monitoring, assessment, and practice tool that supports classroom instruction and guides independent reading. Researchers used a randomized controlled trial to evaluate the program with 344…

  19. Standardized Effect Size Measures for Mediation Analysis in Cluster-Randomized Trials

    ERIC Educational Resources Information Center

    Stapleton, Laura M.; Pituch, Keenan A.; Dion, Eric

    2015-01-01

    This article presents 3 standardized effect size measures to use when sharing results of an analysis of mediation of treatment effects for cluster-randomized trials. The authors discuss 3 examples of mediation analysis (upper-level mediation, cross-level mediation, and cross-level mediation with a contextual effect) with demonstration of the…

  20. Increasing the Degrees of Freedom in Future Group Randomized Trials: The "df*" Method Revisited

    ERIC Educational Resources Information Center

    Murray, David M.; Blitstein, Jonathan L.; Hannan, Peter J.; Shadish, William R.

    2012-01-01

    Background: This article revisits an article published in Evaluation Review in 2005 on sample size estimation and power analysis for group-randomized trials. With help from a careful reader, we learned of an important error in the spreadsheet used to perform the calculations and generate the results presented in that article. As we studied the…

  1. Assessing Impact and Bridging Methodological Divides: Randomized Trials in Countries Affected by Conflict

    ERIC Educational Resources Information Center

    Burde, Dana

    2012-01-01

    Randomized trials have experienced a marked surge in endorsement and popularity in education research in the past decade. This surge reignited paradigm debates and spurred qualitative critics to accuse these experimental designs of eclipsing qualitative research. This article reviews a current iteration of this debate and examines two randomized…

  2. A Randomized Trial of Individual and Couple Behavioral Alcohol Treatment for Women

    ERIC Educational Resources Information Center

    Mccrady, Barbara S.; Epstein, Elizabeth E.; Cook, Sharon; Jensen, Noelle; Hildebrandt, Thomas

    2009-01-01

    Although alcohol use disorders (AUDs) adversely affect women, research on efficacious treatments for women is limited. In this randomized efficacy trial of 102 heterosexual women with AUDs, the authors compared alcohol behavioral couple therapy (ABCT) and alcohol behavioral individual therapy (ABIT) on percentage of days abstinent (PDA) and…

  3. Nasal Oxytocin for Social Deficits in Childhood Autism: A Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Dadds, Mark R.; MacDonald, Elayne; Cauchi, Avril; Williams, Katrina; Levy, Florence; Brennan, John

    2014-01-01

    The last two decades have witnessed a surge in research investigating the application of oxytocin as a method of enhancing social behaviour in humans. Preliminary evidence suggests oxytocin may have potential as an intervention for autism. We evaluated a 5-day "live-in" intervention using a double-blind randomized control trial. 38 male…

  4. Attention Training in Individuals with Generalized Social Phobia: A Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Amir, Nader; Beard, Courtney; Taylor, Charles T.; Klumpp, Heide; Elias, Jason; Burns, Michelle; Chen, Xi

    2009-01-01

    The authors conducted a randomized, double-blind placebo-controlled trial to examine the efficacy of an attention training procedure in reducing symptoms of social anxiety in 44 individuals diagnosed with generalized social phobia (GSP). Attention training comprised a probe detection task in which pictures of faces with either a threatening or…

  5. Design of FRESH START: A Randomized Trial of Exercise and Diet among Cancer Survivors.

    ERIC Educational Resources Information Center

    Demark-Wahnefried, Wendy; Clipp, Elizabeth C.; McBride, Colleen; Lobach, David F.; Lipkus, Isaac; Peterson, Bercedis; Snyder, Denise Clutter; Sloane, Richard; Arbanas, Jennifer; Kraus, William E.

    2003-01-01

    Fresh Start is a randomized, controlled trial that will test whether personally tailored, distance-medicine-based programs will increase exercise and fruit and vegetable consumption and decrease fat intake among individuals recently diagnosed with breast or prostate cancer. People from hospital cancer registries and oncologic practices will…

  6. Fluoxetine, Smoking, and History of Major Depression: A Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Spring, Bonnie; Doran, Neal; Pagoto, Sherry; McChargue, Dennis; Cook, Jessica Werth; Bailey, Katherine; Crayton, John; Hedeker, Donald

    2007-01-01

    The study was a randomized placebo-controlled trial testing whether fluoxetine selectively enhances cessation for smokers with a history of depression. Euthymic smokers with (H+, n = 109) or without (H-, n = 138) a history of major depression received 60 mg fluoxetine or placebo plus group behavioral quit-smoking treatment for 12 weeks. Fluoxetine…

  7. Are Randomized Controlled Trials the (G)old Standard? From Clinical Intelligence to Prescriptive Analytics.

    PubMed

    Van Poucke, Sven; Thomeer, Michiel; Heath, John; Vukicevic, Milan

    2016-01-01

    Despite the accelerating pace of scientific discovery, the current clinical research enterprise does not sufficiently address pressing clinical questions. Given the constraints on clinical trials, for a majority of clinical questions, the only relevant data available to aid in decision making are based on observation and experience. Our purpose here is 3-fold. First, we describe the classic context of medical research guided by Poppers' scientific epistemology of "falsificationism." Second, we discuss challenges and shortcomings of randomized controlled trials and present the potential of observational studies based on big data. Third, we cover several obstacles related to the use of observational (retrospective) data in clinical studies. We conclude that randomized controlled trials are not at risk for extinction, but innovations in statistics, machine learning, and big data analytics may generate a completely new ecosystem for exploration and validation. PMID:27383622

  8. Design and conduct of a large obstetric or neonatal randomized controlled trial.

    PubMed

    Tarnow-Mordi, William; Cruz, Melinda; Morris, Jonathan

    2015-12-01

    As event rates fall, if mortality and disability are to improve further there is increasing need for large, well-designed trials. These should enroll more patients, more rapidly and at lower cost, with better representation of infants at highest risk and greater integration with routine care. This may require simpler datasets, linkage with routinely collected data, and international collaboration. It may be helpful to draw attention to recent evidence that participation in Phase III randomized controlled trials (RCTs) is at least as safe as receiving established care. Nationally coordinated clinical research networks employing local research staff may be the single most effective strategy to integrate clinical trials into routine practice. Other goals are: international standardization of outcomes; consensus on composite endpoints, biomarkers, surrogates and measures of disability; greater efficiency through randomized factorial designs and cluster or cross-over cluster RCTs; and equipping parents as partners in all aspects of the conduct of RCTs and in implementing their results. PMID:26522427

  9. Estimating optimal treatment regimes via subgroup identification in randomized control trials and observational studies.

    PubMed

    Fu, Haoda; Zhou, Jin; Faries, Douglas E

    2016-08-30

    With new treatments and novel technology available, personalized medicine has become an important piece in the new era of medical product development. Traditional statistics methods for personalized medicine and subgroup identification primarily focus on single treatment or two arm randomized control trials. Motivated by the recent development of outcome weighted learning framework, we propose an alternative algorithm to search treatment assignments which has a connection with subgroup identification problems. Our method focuses on applications from clinical trials to generate easy to interpret results. This framework is able to handle two or more than two treatments from both randomized control trials and observational studies. We implement our algorithm in C++ and connect it with R. Its performance is evaluated by simulations, and we apply our method to a dataset from a diabetes study. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26892174

  10. Are Randomized Controlled Trials the (G)old Standard? From Clinical Intelligence to Prescriptive Analytics

    PubMed Central

    2016-01-01

    Despite the accelerating pace of scientific discovery, the current clinical research enterprise does not sufficiently address pressing clinical questions. Given the constraints on clinical trials, for a majority of clinical questions, the only relevant data available to aid in decision making are based on observation and experience. Our purpose here is 3-fold. First, we describe the classic context of medical research guided by Poppers’ scientific epistemology of “falsificationism.” Second, we discuss challenges and shortcomings of randomized controlled trials and present the potential of observational studies based on big data. Third, we cover several obstacles related to the use of observational (retrospective) data in clinical studies. We conclude that randomized controlled trials are not at risk for extinction, but innovations in statistics, machine learning, and big data analytics may generate a completely new ecosystem for exploration and validation. PMID:27383622

  11. Interactive multimedia consent for biobanking: A randomized trial

    PubMed Central

    Simon, Christian M.; Klein, David W.; Schartz, Helen A.

    2015-01-01

    Purpose Interactive multimedia’s potential to improve biobank informed consent has yet to be investigated. The aim of this study was to test the separate effectiveness of interactivity and multimedia at improving participant understanding and confidence of understanding of informed consent, compared to a standard, face-to-face (F2F) biobank consent process. Methods A 2 (F2F versus multimedia) × 2 (standard versus enhanced interactivity) experimental design was used with 200 patients randomly assigned to receive informed consent. All patients received the same information provided in the Biobank’s 9-page consent document. Results Interactivity (F(1,196)=7.56, p=0.007, partial η2=0.037) and Media (F(1,196)=4.27, p=0.04, partial η2=0.021) independently improved participants’ understanding of the Biobank consent. Interactivity (F(1,196) = 6.793, p = 0.01, partial η2=0.033), but not Media (F(1,196) = 0.455, n.s.), resulted in increased participant confidence in their understanding of the Biobank’s consent. Patients took more time to complete the multimedia (M=18.2 min.) than the F2F (M=12.6 min.) conditions. Conclusion This study demonstrated that interactivity and multimedia each can be effective at promoting individuals’ understanding and confidence in understanding of a biobank consent, albeit with additional time investment. Researchers should not assume that multimedia is inherently interactive, but rather separate the two constructs when studying electronic consent. PMID:25834945

  12. Targeting Preschool Children to Promote Cardiovascular Health: Cluster Randomized Trial

    PubMed Central

    Céspedes, Jaime; Briceño, German; Farkouh, Michael E.; Vedanthan, Rajesh; Baxter, Jorge; Leal, Martha; Boffetta, Paolo; Woodward, Mark; Hunn, Marilyn; Dennis, Rodolfo; Fuster, Valentin

    2015-01-01

    BACKGROUND School programs can be effective in modifying knowledge, attitudes, and habits relevant to long-term risk of chronic diseases associated with sedentary lifestyles. As part of a long-term research strategy, we conducted an educational intervention in preschool facilities to assess changes in preschoolers’ knowledge, attitudes, and habits toward healthy eating and living an active lifestyle. METHODS Using a cluster design, we randomly assigned 14 preschool facilities in Bogotá, Colombia to a 5-month educational and playful intervention (7 preschool facilities) or to usual curriculum (7 preschool facilities). A total of 1216 children aged 3–5 years, 928 parents, and 120 teachers participated. A structured survey was used at baseline, at the end of the study, and 12 months later to evaluate changes in knowledge, attitudes, and habits. RESULTS Children in the intervention group showed a 10.9% increase in weighted score, compared with 5.3% in controls. The absolute adjusted difference was 3.90 units (95% confidence interval [CI], 1.64–6.16; P <.001). Among parents, the equivalent statistics were 8.9% and 3.1%, respectively (absolute difference 4.08 units; 95% CI, 2.03 to 6.12; P <.001), and among teachers, 9.4% and 2.5%, respectively (absolute difference 5.36 units; 95% CI, −0.29–11.01; P = .06). In the intervened cohort 1 year after the intervention, children still showed a significant increase in weighted score (absolute difference of 6.38 units; P <.001). CONCLUSIONS A preschool-based intervention aimed at improving knowledge, attitudes, and habits related to healthy diet and active lifestyle is feasible, efficacious, and sustainable in very young children. PMID:23062403

  13. How can good randomized controlled trials in leading journals be so misinterpreted?

    PubMed

    Veith, Frank J

    2013-02-01

    The results of good randomized controlled trials (RCTs) published in leading peer-reviewed journals have been deemed the best possible basis for good medical practice. However, several limitations may decrease their value. These include flaws and weaknesses in the design and the timeliness of RCTs. Progress in a treatment method or control arm may invalidate a trial. So too can defects in patient selection, physician competence, randomization, applicability, end points, and the population being studied. Idiosyncratic flaws can also invalidate an RCT. Examples of these flaws and weaknesses are presented. Another problem with articles describing RCTs is the potential for the conclusions of the trial report to be misleading because of error or bias. This plus subsequent misinterpretation of the trial results or conclusions by others can make the effect of the trial misleading with an unintended detrimental result on medical practice. Guidelines based on such errors or bias-based conclusions and misinterpretations can further compound the problem. This article provides examples of misleading conclusions and/or misinterpretations (spinning) of trial results in articles describing RCTs in leading journals. All physicians should recognize these value-limiting processes so that RCTs can be evaluated adequately and fairly. In that way, they can be used along with good physician judgment to optimize the care delivered to individual patients and to society at large. PMID:23336854

  14. Antibiotic Selection Pressure and Macrolide Resistance in Nasopharyngeal Streptococcus pneumoniae: A Cluster-Randomized Clinical Trial

    PubMed Central

    Skalet, Alison H.; Cevallos, Vicky; Ayele, Berhan; Gebre, Teshome; Zhou, Zhaoxia; Jorgensen, James H.; Zerihun, Mulat; Habte, Dereje; Assefa, Yared; Emerson, Paul M.; Gaynor, Bruce D.; Porco, Travis C.; Lietman, Thomas M.; Keenan, Jeremy D.

    2010-01-01

    Background It is widely thought that widespread antibiotic use selects for community antibiotic resistance, though this has been difficult to prove in the setting of a community-randomized clinical trial. In this study, we used a randomized clinical trial design to assess whether macrolide resistance was higher in communities treated with mass azithromycin for trachoma, compared to untreated control communities. Methods and Findings In a cluster-randomized trial for trachoma control in Ethiopia, 12 communities were randomized to receive mass azithromycin treatment of children aged 1–10 years at months 0, 3, 6, and 9. Twelve control communities were randomized to receive no antibiotic treatments until the conclusion of the study. Nasopharyngeal swabs were collected from randomly selected children in the treated group at baseline and month 12, and in the control group at month 12. Antibiotic susceptibility testing was performed on Streptococcus pneumoniae isolated from the swabs using Etest strips. In the treated group, the mean prevalence of azithromycin resistance among all monitored children increased from 3.6% (95% confidence interval [CI] 0.8%–8.9%) at baseline, to 46.9% (37.5%–57.5%) at month 12 (p = 0.003). In control communities, azithromycin resistance was 9.2% (95% CI 6.7%–13.3%) at month 12, significantly lower than the treated group (p<0.0001). Penicillin resistance was identified in 0.8% (95% CI 0%–4.2%) of isolates in the control group at 1 year, and in no isolates in the children-treated group at baseline or 1 year. Conclusions This cluster-randomized clinical trial demonstrated that compared to untreated control communities, nasopharyngeal pneumococcal resistance to macrolides was significantly higher in communities randomized to intensive azithromycin treatment. Mass azithromycin distributions were given more frequently than currently recommended by the World Health Organization's trachoma program. Azithromycin use in this setting did

  15. Sample size calculations for micro-randomized trials in mHealth.

    PubMed

    Liao, Peng; Klasnja, Predrag; Tewari, Ambuj; Murphy, Susan A

    2016-05-30

    The use and development of mobile interventions are experiencing rapid growth. In "just-in-time" mobile interventions, treatments are provided via a mobile device, and they are intended to help an individual make healthy decisions 'in the moment,' and thus have a proximal, near future impact. Currently, the development of mobile interventions is proceeding at a much faster pace than that of associated data science methods. A first step toward developing data-based methods is to provide an experimental design for testing the proximal effects of these just-in-time treatments. In this paper, we propose a 'micro-randomized' trial design for this purpose. In a micro-randomized trial, treatments are sequentially randomized throughout the conduct of the study, with the result that each participant may be randomized at the 100s or 1000s of occasions at which a treatment might be provided. Further, we develop a test statistic for assessing the proximal effect of a treatment as well as an associated sample size calculator. We conduct simulation evaluations of the sample size calculator in various settings. Rules of thumb that might be used in designing a micro-randomized trial are discussed. This work is motivated by our collaboration on the HeartSteps mobile application designed to increase physical activity. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26707831

  16. A better alternative to stratified permuted block design for subject randomization in clinical trials.

    PubMed

    Zhao, Wenle

    2014-12-30

    Stratified permuted block randomization has been the dominant covariate-adaptive randomization procedure in clinical trials for several decades. Its high probability of deterministic assignment and low capacity of covariate balancing have been well recognized. The popularity of this sub-optimal method is largely due to its simplicity in implementation and the lack of better alternatives. Proposed in this paper is a two-stage covariate-adaptive randomization procedure that uses the block urn design or the big stick design in stage one to restrict the treatment imbalance within each covariate stratum, and uses the biased-coin minimization method in stage two to control imbalances in the distribution of additional covariates that are not included in the stratification algorithm. Analytical and simulation results show that the new randomization procedure significantly reduces the probability of deterministic assignments, and improve the covariate balancing capacity when compared to the traditional stratified permuted block randomization. PMID:25043719

  17. Methodologic issues in terminating enrollment of a subgroup of patients in a multicenter randomized trial.

    PubMed

    Lee, Shing M; Wise, Robert; Sternberg, Alice L; Tonascia, James; Piantadosi, Steven

    2004-01-01

    The National Emphysema Treatment Trial (NETT) was a multicenter randomized controlled trial comparing medical treatment plus lung-volume-reduction surgery (LVRS) to medical treatment alone for the treatment of severe emphysema. The primary outcomes specified for the trial were mortality from all causes and change in functional status as indicated by the change in maximum exercise capacity measured two years after randomization. A secondary objective of the trial was to define criteria to identify subgroups of patients at risk of harm or benefit from LVRS. Stopping guidelines for safety and efficacy based on 30-day mortality and a combination of overall mortality and functional status at two years were specified at the inception of the trial. Although specific subgroups of patients likely to benefit were not identified in advance, several clinical factors were specified as likely to be important in defining subgroups with differential outcome. In May 2001, with 40% of expected deaths accrued, the Data and Safety Monitoring Board determined that a subgroup of patients was at significantly higher risk of 30-day mortality from LVRS without counterbalancing evidence of functional benefit, and recommended that the protocol be modified to exclude further randomization of such patients. The trial's sponsor, the National Heart, Lung and Blood Institute, accepted the recommendation, which was rapidly communicated to participating clinics. This paper describes the operational aspects of identification of the subgroup and implementation of the recommendation to continue the trial, but to terminate enrollment of new patients in the subgroup. These aspects include notification of the investigators, the institutional review boards, the Research Group, the patients and the medical community. We also describe the repercussions of the publication and the misinterpretations of the results based on media coverage. PMID:16279258

  18. A pilot test of the new Swiss regulatory procedure for categorizing clinical trials by risk: A randomized controlled trial

    PubMed Central

    Cevallos, Myriam; Züllig, Stephanie; Christen, Andri; Meier, Brigitte E; Goetz, Martin; Coslovsky, Michael; Trelle, Sven

    2015-01-01

    Background/Aims: Several countries are working to adapt clinical trial regulations to align the approval process to the level of risk for trial participants. The optimal framework to categorize clinical trials according to risk remains unclear, however. Switzerland is the first European country to adopt a risk-based categorization procedure in January 2014. We assessed how accurately and consistently clinical trials are categorized using two different approaches: an approach using criteria set forth in the new law (concept) or an intuitive approach (ad hoc). Methods: This was a randomized controlled trial with a method-comparison study nested in each arm. We used clinical trial protocols from eight Swiss ethics committees approved between 2010 and 2011. Protocols were randomly assigned to be categorized in one of three risk categories using the concept or the ad hoc approach. Each protocol was independently categorized by the trial’s sponsor, a group of experts and the approving ethics committee. The primary outcome was the difference in categorization agreement between the expert group and sponsors across arms. Linear weighted kappa was used to quantify agreements, with the difference between kappas being the primary effect measure. Results: We included 142 of 231 protocols in the final analysis (concept = 78; ad hoc = 64). Raw agreement between the expert group and sponsors was 0.74 in the concept and 0.78 in the ad hoc arm. Chance-corrected agreement was higher in the ad hoc (kappa: 0.34 (95% confidence interval = 0.10–0.58)) than in the concept arm (0.27 (0.06–0.50)), but the difference was not significant (p = 0.67). Limitations: The main limitation was the large number of protocols excluded from the analysis mostly because they did not fit with the clinical trial definition of the new law. Conclusion: A structured risk categorization approach was not better than an ad hoc approach. Laws introducing risk-based approaches should provide guidelines

  19. Spatiotemporal dynamics of random stimuli account for trial-to-trial variability in perceptual decision making

    PubMed Central

    Park, Hame; Lueckmann, Jan-Matthis; von Kriegstein, Katharina; Bitzer, Sebastian; Kiebel, Stefan J.

    2016-01-01

    Decisions in everyday life are prone to error. Standard models typically assume that errors during perceptual decisions are due to noise. However, it is unclear how noise in the sensory input affects the decision. Here we show that there are experimental tasks for which one can analyse the exact spatio-temporal details of a dynamic sensory noise and better understand variability in human perceptual decisions. Using a new experimental visual tracking task and a novel Bayesian decision making model, we found that the spatio-temporal noise fluctuations in the input of single trials explain a significant part of the observed responses. Our results show that modelling the precise internal representations of human participants helps predict when perceptual decisions go wrong. Furthermore, by modelling precisely the stimuli at the single-trial level, we were able to identify the underlying mechanism of perceptual decision making in more detail than standard models. PMID:26752272

  20. Spatiotemporal dynamics of random stimuli account for trial-to-trial variability in perceptual decision making.

    PubMed

    Park, Hame; Lueckmann, Jan-Matthis; von Kriegstein, Katharina; Bitzer, Sebastian; Kiebel, Stefan J

    2016-01-01

    Decisions in everyday life are prone to error. Standard models typically assume that errors during perceptual decisions are due to noise. However, it is unclear how noise in the sensory input affects the decision. Here we show that there are experimental tasks for which one can analyse the exact spatio-temporal details of a dynamic sensory noise and better understand variability in human perceptual decisions. Using a new experimental visual tracking task and a novel Bayesian decision making model, we found that the spatio-temporal noise fluctuations in the input of single trials explain a significant part of the observed responses. Our results show that modelling the precise internal representations of human participants helps predict when perceptual decisions go wrong. Furthermore, by modelling precisely the stimuli at the single-trial level, we were able to identify the underlying mechanism of perceptual decision making in more detail than standard models. PMID:26752272

  1. Pragmatic randomized trials in drug development pose new ethical questions: a systematic review.

    PubMed

    Kalkman, Shona; van Thiel, Ghislaine J M W; Grobbee, Diederick E; van Delden, Johannes J M

    2015-07-01

    Implementation of pragmatic design elements in drug development could bridge the evidence gap that currently exists between the knowledge we have regarding the efficacy of a drug versus its true, comparative effectiveness in real life. We performed a review of the literature to identify the ethical challenges thus far related to pragmatic trials. The three central ethical questions identified for pragmatic trials are: (i) what level of oversight should pragmatic trials require; (ii) do randomized patients face additional risks; and (iii) is a waiver of informed consent ethically defensible? Despite the fact all reviewed publications dealt with post-launch pragmatic trials, these results could serve as an important starting point for conceptualizing which challenges could potentially arise in the pre-launch setting. PMID:25794600

  2. The relaxation exercise and social support trial-resst: study protocol for a randomized community based trial

    PubMed Central

    2011-01-01

    Background Studies suggests a possible link between vaginal discharge and common mental distress, as well as highlight the implications of the subjective burden of disease and its link with mental health. Methods/Design This is a community-based intervention trial that aims to evaluate the impact of a psycho-social intervention on medically unexplained vaginal discharge (MUVD) in a group of married, low-income Lebanese women, aged 18-49, and suffering from low to moderate levels of anxiety and/or depression. The intervention consisted of 12 sessions of structured social support, problem solving techniques, group discussions and trainer-supervised relaxation exercises (twice per week over six weeks). Women were recruited from Hey el Selloum, a southern disadvantaged suburb of Beirut, Lebanon, during an open recruitment campaign. The primary outcome was self-reported MUVD, upon ruling out reproductive tract infections (RTIs), through lab analysis. Anxiety and/or depression symptoms were the secondary outcomes for this trial. These were assessed using an Arabic validated version of the Hopkins Symptoms Checklist-25 (HSCL-25). Assessments were done at baseline and six months using face-to face interviews, pelvic examinations and laboratory tests. Women were randomized into either intervention or control group. Intent to treat analysis will be used. Discussion The results will indicate whether the proposed psychosocial intervention was effective in reducing MUVD (possibly mediated by common mental distress). Trial Registration The trial is registered at the Wellcome Trust Registry, ISRCTN assigned: ISRCTN: ISRCTN98441241 PMID:21864414

  3. Multivitamins in the Prevention of Cancer in Men: The Physicians’ Health Study II Randomized Controlled Trial

    PubMed Central

    Gaziano, J. Michael; Sesso, Howard D.; Christen, William G.; Bubes, Vadim; Smith, Joanne P.; MacFadyen, Jean; Schvartz, Miriam; Manson, JoAnn E.; Glynn, Robert J.; Buring, Julie E.

    2012-01-01

    Context Multivitamin preparations are the most common dietary supplement, taken by at least one-third of all US adults. Limited observational studies have not provided evidence regarding associations of multivitamin use with total and site-specific cancer incidence or mortality. Objective To determine whether long-term multivitamin supplementation decreases the risk of total and site-specific cancer events among men. Design The Physicians’ Health Study II is a randomized, double-blind, placebo-controlled trial of a common multivitamin that began in 1997 with treatment and follow-up through June 1, 2011. Setting and Participants A total of 14,641 male U.S. physicians initially aged ≥50 years (mean [± SD] age; 64.3 [± 9.2] years), including 1,312 men with a history of cancer at randomization, were enrolled. Intervention Daily multivitamin, as Centrum Silver. Main Outcome Measures A primary outcome was total cancer (excluding non-melanoma skin cancer), with prostate, colorectal, and other site-specific cancers among secondary endpoints included in this report. Results During a median (interquartile range) follow-up of 11.2 (10.7 to 13.3) years, there were 2,669 men with confirmed cancer, including 1,373 cases of prostate cancer and 210 cases of colorectal cancer. Compared with placebo, men taking a daily multivitamin had a statistically significant reduction in the incidence of total cancer (active and placebo multivitamin groups, 17.0 and 18.3 events, respectively, per 1,000 person-years; hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.86–0.998; P=0.044). There was no significant effect of a daily multivitamin on prostate cancer (HR, 0.98; 95% CI, 0.88–1.09; P=0.76), colorectal cancer (HR, 0.89; 95% CI, 0.68–1.17; P=0.39), or other site-specific cancers There was a lower risk of cancer mortality that did not reach statistical significance (HR, 0.88; 95% CI, 0.77–1.01; P=0.07). Daily multivitamin use was associated with a reduction in total

  4. A randomized trial of plasmapheresis and subsequent pulse cyclophosphamide in severe lupus: design of the LPSG trial.

    PubMed

    Euler, H H; Schroeder, J O; Zeuner, R A; Teske, E

    1991-10-01

    A group of clinics cooperating as the Lupus Plasmapheresis Study Group (LPSG) is starting an international multicenter study of the treatment of severe systemic lupus erythematosus. The primary goal of this randomized and prospective trial is to establish whether treatment with plasmapheresis and subsequent pulse cyclophosphamide improves the outcome compared to treatment with pulse cyclophosphamide alone. The underlying rationale assumes that plasmapheresis: a) eliminates pathogenic autoantibodies and immune complexes and b) induces a compensatory activation of pathogenic lymphocyte clones through a feed-back between circulating antibodies and their respective antibody-producing clones. Synchronization of plasmapheresis with subsequent pulse cyclophosphamide should enhance the deletion of pathogenic clones during the period of greatest vulnerability. This overview reviews the first results of treatment approaches based on this concept and summarizes the design of the LPSG trial. PMID:1748532

  5. Multicenter randomized trial of cell therapy in cardiopathies – MiHeart Study

    PubMed Central

    Tura, Bernardo R; Martino, Helena F; Gowdak, Luis H; dos Santos, Ricardo Ribeiro; Dohmann, Hans F; Krieger, José E; Feitosa, Gilson; Vilas-Boas, Fábio; Oliveira, Sérgio A; Silva, Suzana A; Bozza, Augusto Z; Borojevic, Radovan; de Carvalho, Antonio C Campos

    2007-01-01

    Background Cardiovascular diseases are the major cause of death in the world. Current treatments have not been able to reverse this scenario, creating the need for the development of new therapies. Cell therapies have emerged as an alternative for cardiac diseases of distinct causes in experimental animal studies and more recently in clinical trials. Method/Design We have designed clinical trials to test for the efficacy of autologous bone marrow derived mononuclear cell therapies in four different cardiopathies: acute and chronic ischemic heart disease, and Chagasic and dilated cardiomyopathy. All trials are multicenter, randomized, double-blind and placebo controlled. In each trial 300 patients will be enrolled and receive optimized therapy for their specific condition. Additionally, half of the patients will receive the autologous bone marrow cells while the other half will receive placebo (saline with 5% autologous serum). For each trial there are specific inclusion and exclusion criteria and the method for cell delivery is intramyocardial for the chronic ischemic heart disease and intracoronary for all others. Primary endpoint for all studies will be the difference in ejection fraction (determined by Simpson's rule) six and twelve months after intervention in relation to the basal ejection fraction. The main hypothesis of this study is that the patients who receive the autologous bone-marrow stem cell implant will have after a 6 month follow-up a mean increase of 5% in absolute left ventricular ejection fraction in comparison with the control group. Discussion Many phase I clinical trials using cell therapy for cardiac diseases have already been performed. The few randomized studies have yielded conflicting results, rendering necessary larger well controlled trials to test for efficacy of cell therapies in cardiopathies. The trials registration numbers at the NIH registry are the following: Chagasic cardiomyopathy (NCT00349271), dilated cardiomyopathy (NCT

  6. Beautiful small: Misleading large randomized controlled trials? The example of colloids for volume resuscitation.

    PubMed

    Wiedermann, Christian J; Wiedermann, Wolfgang

    2015-01-01

    In anesthesia and intensive care, treatment benefits that were claimed on the basis of small or modest-sized trials have repeatedly failed to be confirmed in large randomized controlled trials. A well-designed small trial in a homogeneous patient population with high event rates could yield conclusive results; however, patient populations in anesthesia and intensive care are typically heterogeneous because of comorbidities. The size of the anticipated effects of therapeutic interventions is generally low in relation to relevant endpoints. For regulatory purposes, trials are required to demonstrate efficacy in clinically important endpoints, and therefore must be large because clinically important study endpoints such as death, sepsis, or pneumonia are dichotomous and infrequently occur. The rarer endpoint events occur in the study population; that is, the lower the signal-to-noise ratio, the larger the trials must be to prevent random events from being overemphasized. In addition to trial design, sample size determination on the basis of event rates, clinically meaningful risk ratio reductions and actual patient numbers studied are among the most important characteristics when interpreting study results. Trial size is a critical determinant of generalizability of study results to larger or general patient populations. Typical characteristics of small single-center studies responsible for their known fragility include low variability of outcome measures for surrogate parameters and selective publication and reporting. For anesthesiology and intensive care medicine, findings in volume resuscitation research on intravenous infusion of colloids exemplify this, since both the safety of albumin infusion and the adverse effects of the artificial colloid hydroxyethyl starch have been confirmed only in large-sized trials. PMID:26330723

  7. Beautiful small: Misleading large randomized controlled trials? The example of colloids for volume resuscitation

    PubMed Central

    Wiedermann, Christian J; Wiedermann, Wolfgang

    2015-01-01

    In anesthesia and intensive care, treatment benefits that were claimed on the basis of small or modest-sized trials have repeatedly failed to be confirmed in large randomized controlled trials. A well-designed small trial in a homogeneous patient population with high event rates could yield conclusive results; however, patient populations in anesthesia and intensive care are typically heterogeneous because of comorbidities. The size of the anticipated effects of therapeutic interventions is generally low in relation to relevant endpoints. For regulatory purposes, trials are required to demonstrate efficacy in clinically important endpoints, and therefore must be large because clinically important study endpoints such as death, sepsis, or pneumonia are dichotomous and infrequently occur. The rarer endpoint events occur in the study population; that is, the lower the signal-to-noise ratio, the larger the trials must be to prevent random events from being overemphasized. In addition to trial design, sample size determination on the basis of event rates, clinically meaningful risk ratio reductions and actual patient numbers studied are among the most important characteristics when interpreting study results. Trial size is a critical determinant of generalizability of study results to larger or general patient populations. Typical characteristics of small single-center studies responsible for their known fragility include low variability of outcome measures for surrogate parameters and selective publication and reporting. For anesthesiology and intensive care medicine, findings in volume resuscitation research on intravenous infusion of colloids exemplify this, since both the safety of albumin infusion and the adverse effects of the artificial colloid hydroxyethyl starch have been confirmed only in large-sized trials. PMID:26330723

  8. An Evaluation of the Effectiveness of Recruitment Methods: The Staying Well after Depression Randomized Controlled Trial

    PubMed Central

    Krusche, Adele; Rudolf von Rohr, Isabelle; Muse, Kate; Duggan, Danielle; Crane, Catherine; Williams, J. Mark G.

    2014-01-01

    Background Randomized controlled trials (RCTs) are widely accepted as being the most efficient way of investigating the efficacy of psychological therapies. However, researchers conducting RCTs commonly report difficulties recruiting an adequate sample within planned timescales. In an effort to overcome recruitment difficulties, researchers often are forced to expand their recruitment criteria or extend the recruitment phase, thus increasing costs and delaying publication of results. Research investigating the effectiveness of recruitment strategies is limited and trials often fail to report sufficient details about the recruitment sources and resources utilised. Purpose We examined the efficacy of strategies implemented during the Staying Well after Depression RCT in Oxford to recruit participants with a history of recurrent depression. Methods We describe eight recruitment methods utilised and two further sources not initiated by the research team and examine their efficacy in terms of (i) the return, including the number of potential participants who contacted the trial and the number who were randomized into the trial, (ii) cost-effectiveness, comprising direct financial cost and manpower for initial contacts and randomized participants, and (iii) comparison of sociodemographic characteristics of individuals recruited from different sources. Results Poster advertising, web-based advertising and mental health worker referrals were the cheapest methods per randomized participant; however, the ratio of randomized participants to initial contacts differed markedly per source. Advertising online, via posters and on a local radio station were the most cost-effective recruitment methods for soliciting participants who subsequently were randomized into the trial. Advertising across many sources (saturation) was found to be important. Limitations It may not be feasible to employ all the recruitment methods used in this trial to obtain participation from other

  9. Emotionally Focused Interventions for Couples with Chronically Ill Children: A 2-Year Follow-Up

    ERIC Educational Resources Information Center

    Cloutier, Paula F.; Manion, Ian G.; Walker, Jan Gordon; Johnson, Susan M.

    2002-01-01

    Couples with chronically ill children are particularly at risk for experiencing marital distress. The study presented here is a 2-year follow-up of a randomized control trial that assessed the efficacy of Emotionally Focused Therapy (EFT) in decreasing marital distress in a sample of couples with a chronically ill child. Thirteen couples with…

  10. MST with Conduct Disordered Youth in Sweden: Costs and Benefits after 2 Years

    ERIC Educational Resources Information Center

    Olsson, Tina M.

    2010-01-01

    Objectives: The purpose of this study was to investigate the costs and benefits associated with multisystemic therapy (MST) for conduct disordered youth, 2 years following intake. Methods: The study employed a secondary analysis of 156 youth enrolled in a randomized trial assessing the psychosocial and behavioral outcomes of MST. Results: MST cost…

  11. Randomized trials of dichlorphenamide in the periodic paralyses. Working Group on Periodic Paralysis.

    PubMed

    Tawil, R; McDermott, M P; Brown, R; Shapiro, B C; Ptacek, L J; McManis, P G; Dalakas, M C; Spector, S A; Mendell, J R; Hahn, A F; Griggs, R C

    2000-01-01

    Although the carbonic anhydrase inhibitors have been used in the treatment of the primary periodic paralyses (PPs), their efficacy has not been demonstrated in double-blind, placebo-controlled trials. Therefore, we tested the efficacy of dichlorphenamide (DCP; Daranide), a potent carbonic anhydrase inhibitor, in the treatment of episodic weakness in the primary PPs. We performed two multicenter, randomized, double-blind, placebo-controlled crossover trials, one involving 42 subjects with hypokalemic periodic paralysis (HypoPP) and the other involving 31 subjects with potassium-sensitive periodic paralysis (PSPP). In each trial, two 8-week treatment periods were separated by an active washout period of at least 9 weeks. The primary outcome variable in the HypoPP trial was the occurrence of an intolerable increase in attack severity or frequency (end point). The primary outcome variable in the PSPP trial was the number of attacks per week. In the HypoPP trial, there were 13 subjects who exhibited a preference (in terms of the end point) for either DCP or placebo, and 11 of these preferred DCP. In the PSPP trial, DCP significantly reduced attack rates relative to placebo. DCP also significantly reduced attack rates relative to placebo in the HypoPP subjects. We conclude that DCP is effective in the prevention of episodic weakness in both HypoPP and PSPP. PMID:10632100

  12. A Blinded Randomized Controlled Trial of Motivational Interviewing to Improve Adherence with Osteoporosis Medications: Design of the OPTIMA Trial

    PubMed Central

    Solomon, Daniel H.; Gleeson, Timothy; Iversen, Maura; Avorn, Jerome; Brookhart, M. Alan; Lii, Joyce; Losina, Elena; May, Frank; Patrick, Amanda; Shrank, William H.; Katz, Jeffrey N.

    2010-01-01

    Purpose While many effective treatments exist for osteoporosis, most people do not adhere to such treatments long-term. No proven interventions exist to improve osteoporosis medication adherence. We report here on the design and initial enrollment in an innovative randomized controlled trial aimed at improving adherence to osteoporosis treatments. Methods The trial represents a collaboration between academic researchers and a state-run pharmacy benefits program for low-income older adults. Beneficiaries beginning treatment with a medication for osteoporosis are targeted for recruitment. We randomize consenting individuals to receive 12-months of mailed education (control arm) or an intervention consisting of one-on-one telephone-based counseling and the mailed education. Motivational Interviewing forms the basis for the counseling program which is delivered by seven trained and supervised health counselors over ten telephone calls. The counseling sessions include scripted dialogue, open-ended questions about medication adherence and its barriers, as well as structured questions. The primary endpoint of the trial is medication adherence measured over the 12-month intervention period. Secondary endpoints include fractures, nursing home admissions, health care resource utilization, and mortality. Results During the first 7 months of recruitment, we have screened 3,638 potentially eligible subjects. After an initial mailing, 1,115 (30.6%) opted out of telephone recruitment and 1,019 (28.0%) could not be successfully contacted. Of the remaining, 879 (24.2%) consented to participate and were randomized. Women comprise over 90% of all groups, mean ages range from 77–80 years old, and the majority in all groups was white. The distribution of osteoporosis medications was comparable across groups and the median number of different prescription drugs used in the prior year was 8–10. Conclusions We have developed a novel intervention for improving osteoporosis medication

  13. Pilot study evaluating broccoli sprouts in advanced pancreatic cancer (POUDER trial) - study protocol for a randomized controlled trial

    PubMed Central

    2014-01-01

    Background Pancreatic ductal adenocarcinoma (PDA) is one of the most aggressive malignancies with marked resistance to chemo- and radiotherapy. PDA-cancer stem cells (CSCs) are not targeted by current therapies and may be a reason for poor prognosis. Studies indicate that diets rich in cabbage, broccoli, and cauliflower offer cancer preventative and therapeutic benefits. Recent experimental studies have confirmed these findings and demonstrated that isothiocyanate, sulforaphane, and the polyphenol, quercetin, effectively reduced tumor growth and enhanced the sensitivity of the cancer cells to current chemotherapeutics. The aim of the present study is to test the feasibility of a randomized controlled trial on the application of freeze-dried broccoli sprouts in patients with advanced PDA. Methods and study design The study is designed as a prospective randomized, double-blinded pilot trial with a treatment and a placebo-controlled arm in a single center setting. A total number of forty patients (18 years or older) in two parallel groups with advanced, surgically non-resectable PDA under palliative chemotherapy are planned for recruitment. Patients in the treatment group will receive fifteen capsules of the study substance per day (90 mg of active sulforaphane) during the chemotherapy treatment course. Patients in the placebo group will receive the same capsule size and portion distribution with inactive substances (mainly methylcellulose). The follow-up duration is one year. Feasibility of the study substance, adverse effects, and patient compliance, as well as levels of serum tumor markers (CEA, CA 19-9), quality of life, and patient overall survival rates will be assessed at defined points of time. Discussion The POUDER trial is expected to transfer promising experimental and epidemiological data into a clinical pilot study to assess the effectiveness of broccoli sprout extracts in the treatment of advanced PDA. The study objectives will provide data on the

  14. Randomized trials of high-dose chemotherapy in breast cancer: fraud, the press and the data (or lessons learned in medical policy governing clinical research).

    PubMed Central

    Antman, Karen

    2002-01-01

    High dose therapy for breast cancer remains controversial. Of the 15 randomized trials of high dose therapy in breast cancer reported to date, two South African studies have been discredited leaving 13 remaining studies. Mortality was consistently low, in the 0 to 2.5% range, except for the BCNU containing American Intergroup study, which had a 7.4% toxic mortality rate. Seven of the remaining 13 studies randomized fewer than 200 patients. Three of these small studies have significant differences in disease free survival, and a fourth study has a trend in favor of high dose therapy. The other three small studies cannot exclude a survival difference of 20%. Of the 6 remaining moderately large trials of 219 to 885 randomized patients, 5 are adjuvant studies and one included patients with metastatic disease. Of the five adjuvant trials, four have significant differences in relapse rate favoring the high dose arm, and the remaining study has a trend (with a high dose sequential single agent design rather than combination therapy as in the other studies). A planned subset analysis of the first 284 patients in the largest study funded by the Dutch insurance industry showed a significant advantage for high dose therapy. Given the 2-year median time to relapse and an addition 2-year median to death after relapse, the follow up for survival of 3-5 years on these studies is still short. In the only moderately sized metastatic trial from the National Cancer Institute of Canada with a very short median follow-up of 19 months, a significant difference in disease free survival has emerged, with no difference in survival. PMID:12053718

  15. Defining a Clinically Meaningful Effect for the Design and Interpretation of Randomized Controlled Trials

    PubMed Central

    Kraemer, Helena C.; Epstein, Robert S.; Frank, Ellen; Haynes, Ginger; Laughren, Thomas P.; Mcnulty, James; Reed, Shelby D.; Sanchez, Juan; Leon, Andrew C.

    2013-01-01

    Objective: This article captures the proceedings of a meeting aimed at defining clinically meaningful effects for use in randomized controlled trials for psychopharmacological agents. Design: Experts from a variety of disciplines defined clinically meaningful effects from their perspectives along with viewpoints about how to design and interpret randomized controlled trials. Setting: The article offers relevant, practical, and sometimes anecdotal information about clinically meaningful effects and how to interpret them. Participants: The concept for this session was the work of co-chairs Richard Keefe and the late Andy Leon. Faculty included Richard Keefe, PhD; James McNulty, AbScB; Robert S. Epstein, MD, MS; Shelby D. Reed, PhD; Juan Sanchez, MD; Ginger Haynes, PhD; Andrew C. Leon, PhD; Helena Chmura Kraemer, PhD; Ellen Frank, PhD, and Kenneth L. Davis, MD. Results: The term clinically meaningful effect is an important aspect of designing and interpreting randomized controlled trials but can be particularly difficult in the setting of psychopharmacology where effect size may be modest, particularly over the short term, because of a strong response to placebo. Payers, regulators, patients, and clinicians have different concerns about clinically meaningful effects and may describe these terms differently. The use of moderators in success rate differences may help better delineate clinically meaningful effects. Conclusion: There is no clear consensus on a single definition for clinically meaningful differences in randomized controlled trials, and investigators must be sensitive to specific concerns of stakeholders in psychopharmacology in order to design and execute appropriate clinical trials. PMID:23882433

  16. Feasibility of a Randomized Clinical Trial for Treatment of Femoroacetabular Impingement of the Hip

    PubMed Central

    Boye, Gloria N.; Murray, Kerri; Clohisy, John C.; Kim, Young-Jo

    2015-01-01

    Background: Symptomatic femoroacetabular impingement (FAI) is currently corrected by surgery. However, it is possible that nonsurgical treatment could resolve symptomatic FAI in some patients; thus, uncertainty about the necessity of surgical treatment exists. The current equipoise concerning FAI treatment presents an opportunity to conduct a randomized controlled trial (RCT) of surgical and nonsurgical treatment options. Given the unique challenge of adequate patient enrollment in RCTs, it is important that a preliminary study is done to appraise the feasibility of conducting an RCT. Purpose: To estimate enrollment rates of a planned future RCT to compare surgical and nonsurgical treatments for symptomatic FAI and to identify factors associated with patients’ willingness to participate in the randomized trial. Study Design: Cross-sectional study; Level of evidence, 4. Methods: Patients diagnosed with FAI at 2 orthopaedic centers were presented with a hypothetical randomized trial comparing 2 treatment options for FAI. All patients completed forms providing information regarding their willingness to participate and treatment preferences. Results: A total of 75 patients participated in the study: 53 and 22 from 2 centers, respectively. Twenty-eight percent indicated absolute willingness to participate in the trial, 40% were probably willing or unsure, and 32% were definitely not willing; 18.7% had a strong preference for surgery while 2.7% strongly preferred nonsurgical treatment. The majority (78.6%) had no strong preference for either treatment arm. There were correlations between treatment preferences and willingness to participate. Patients with a strong treatment preference and/or a preference for surgery were less likely to be willing to participate. Conclusion: The study findings suggest that sufficient patient accrual for a randomized trial of FAI treatment is currently feasible while equipoise still exists among patients and surgeons. PMID:26673688

  17. Dressing wear time after breast reconstruction: study protocol for a randomized controlled trial

    PubMed Central

    2013-01-01

    Background One of the major risk variables for surgical site infection is wound management. Understanding infection risk factors for breast operations is essential in order to develop infection-prevention strategies and improve surgical outcomes. The aim of this trial is to assess the influence of dressing wear time on surgical site infection rates and skin colonization. Patients’ perception at self-assessment will also be analyzed. Methods/Design This is a two-arm randomized controlled trial. Two hundred breast cancer patients undergoing immediate or delayed breast reconstruction will be prospectively enrolled. Patients will be randomly allocated to group I (dressing removed on postoperative day one) or group II (dressing removed on postoperative day six). Surgical site infections will be defined by standard criteria from the Centers for Disease Control and Prevention (CDC). Skin colonization will be assessed by culture of samples collected at predefined time points. Patients will score dressing wear time with regard to safety, comfort and convenience. Discussion The evidence to support dressing standards for breast surgery wounds is empiric and scarce. CDC recommends protecting, with a sterile dressing for 24 to 48 hours postoperatively, a primarily closed incision, but there is no recommendation to cover this kind of incision beyond 48 hours, or on the appropriate time to shower or bathe with an uncovered incision. The results of the ongoing trial may support standard recommendations regarding dressing wear time after breast reconstruction. Trial registration ClinicalTrials.gov identifier: http://NCT01148823. PMID:23432779

  18. Acupuncture for acute stroke: study protocol for a multicenter, randomized, controlled trial

    PubMed Central

    2014-01-01

    Background Acupuncture has been widely used as a treatment for stroke in China for more than 3,000 years. However, previous research has not yet shown that acupuncture is effective as a stroke treatment. We report a protocol for a multicenter, randomized, controlled, and outcome assessor-blind trial to evaluate the efficacy and safety of acupuncture on acute ischemic stroke. Methods/Design In a prospective trial involving three hospitals in the Zhejiang Province (China) 250 patients with a recent (less than 1 week previous) episode of ischemic stroke will be included. Patients will be randomized into two groups: an acupuncture group given scalp acupuncture and electroacupuncture, and a control group given no acupuncture. Eighteen treatment sessions will be performed over a three-week period. The primary outcome will be measured by changes in the National Institutes of Health Stroke Scale score at the one, three, and four-week follow-up. Secondary outcome measures will be: 1) the Fugl-Meyer assessment scale for motor function; 2) the mini-mental state examination and Montreal cognitive assessment for cognitive function; 3) the video-fluoroscopic swallowing study for swallowing ability; and 4) the incidence of adverse events. Discussion This trial is expected to clarify whether or not acupuncture is effective for acute stroke. It will also show if acupuncture can improve motor, cognitive, or swallowing function. Trial registration Chinese Clinical Trial Registry ChiCTR-TRC-12001971. PMID:24908241

  19. Traumeel S® for pain relief following hallux valgus surgery: a randomized controlled trial

    PubMed Central

    2010-01-01

    Background In spite of recent advances in post-operative pain relief, pain following orthopedic surgery remains an ongoing challenge for clinicians. We examined whether a well known and frequently prescribed homeopathic preparation could mitigate post-operative pain. Method We performed a randomized, double blind, placebo-controlled trial to evaluate the efficacy of the homeopathic preparation Traumeel S® in minimizing post-operative pain and analgesic consumption following surgical correction of hallux valgus. Eighty consecutive patients were randomized to receive either Traumeel tablets or an indistinguishable placebo, and took primary and rescue oral analgesics as needed. Maximum numerical pain scores at rest and consumption of oral analgesics were recorded on day of surgery and for 13 days following surgery. Results Traumeel was not found superior to placebo in minimizing pain or analgesic consumption over the 14 days of the trial, however a transient reduction in the daily maximum post-operative pain score favoring the Traumeel arm was observed on the day of surgery, a finding supported by a treatment-time interaction test (p = 0.04). Conclusions Traumeel was not superior to placebo in minimizing pain or analgesic consumption over the 14 days of the trial. A transient reduction in the daily maximum post-operative pain score on the day of surgery is of questionable clinical importance. Trial Registration This study was registered at ClinicalTrials.gov. # NCT00279513 PMID:20380750

  20. Global Postural Reeducation for patients with musculoskeletal conditions: a systematic review of randomized controlled trials

    PubMed Central

    Ferreira, Giovanni E.; Barreto, Rodrigo G. P.; Robinson, Caroline C.; Plentz, Rodrigo D. M.; Silva, Marcelo F.

    2016-01-01

    ABSTRACT Objectives To systematically review randomized controlled trials that assessed the effects of Global Postural Reeducation (GPR) on patient-reported outcomes in conditions of the musculoskeletal system. Method An electronic search of MEDLINE (via PubMed), EMBASE, Cochrane CENTRAL, and SciELO was performed from their inception to June 2015. Randomized controlled trials that analyzed pain and patient-reported outcomes were included in this review. The Cochrane Collaboration’s Risk of Bias Tool was used to evaluate risk of bias, and the quality of evidence was rated following the GRADE approach. There were no language restrictions. Results Eleven trials were included totaling 383 patients. Overall, the trials had high risk of bias. GPR was superior to no treatment but not to other forms of treatment for pain and disability. No placebo-controlled trials were found. Conclusion GPR is not superior to other treatments; however, it is superior to no treatment. Due to the lack of studies, it is unknown if GPR is better than placebo. The quality of the available evidence ranges from low to very low, therefore future studies may change the effect estimates of GPR in musculoskeletal conditions. PMID:27437710