The Experts below are selected from a list of 9450 Experts worldwide ranked by ideXlab platform
Stig Brorson - One of the best experts on this subject based on the ideXlab platform.
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Observer Bias in randomized clinical trials with time to event outcomes systematic review of trials with both blinded and non blinded outcome assessors
International Journal of Epidemiology, 2014Co-Authors: Asbjørn Hróbjartsson, Ann Sofia Skou Thomsen, Frida Emanuelsson, Britta Tendal, Jeppe Vejlgaard Rasmussen, Jorgen Hilden, Isabelle Boutron, Philippe Ravaud, Stig BrorsonAbstract:Background: We wanted to evaluate the impact of nonblinded outcome assessors on estimated treatment effects in time-to-event trials. Methods: Systematic review of randomized clinical trials with both blinded and nonblinded assessors of the same time-to-event outcome. Two authors agreed on inclusion of trials and outcomes. We compared hazard ratios based on nonblinded and blinded assessments. A ratio of hazard ratios (RHR) <1 indicated that nonblinded assessors generated more optimistic effect estimates. We pooled RHRs with inverse variance randomeffects meta-analysis. Results: We included 18 trials. Eleven trials (1969 patients) with subjective outcomes provided hazard ratios, RHR 0.88 (0.69 to 1.12), (I 2 ¼44%, P ¼0.06), but unconditional pooling was problematic because of qualitative heterogeneity. Four atypical cytomegalovirus retinitis trials compared experimental oral administration with control intravenous administration of the same drug, resulting in Bias favouring the control intervention, RHR 1.33 (0.98 to 1.82). Seven trials of cytomegalovirus retinitis, tibial fracture and multiple sclerosis compared experimental interventions with standard control interventions, e.g. placebo, no-treatment or active control, resulting in Bias favouring the experimental intervention, RHR 0.73 (0.57 to 0.93), indicating an average exaggeration of nonblinded hazard ratios by 27% (7% to 43%). Conclusions: Lack of blinded outcome assessors in randomized trials with subjective time-to-event outcomes causes high risk of Observer Bias. Nonblinded outcome
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Observer Bias in randomized clinical trials with measurement scale outcomes: a systematic review of trials with both blinded and nonblinded assessors
Canadian Medical Association Journal, 2013Co-Authors: Asbjørn Hróbjartsson, Ann Sofia Skou Thomsen, Frida Emanuelsson, Britta Tendal, Jorgen Hilden, Isabelle Boutron, Philippe Ravaud, Stig BrorsonAbstract:Background: Clinical trials are commonly done without blinded outcome assessors despite the risk of Bias. We wanted to evaluate the effect of nonblinded outcome assessment on estimated effects in randomized clinical trials with outcomes that involved subjective measurement scales. Methods: We conducted a systematic review of randomized clinical trials with both blinded and nonblinded assessment of the same measurement scale outcome. We searched PubMed, EMBASE, PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials, HighWire Press and Google Scholar for relevant studies. Two investigators agreed on the inclusion of trials and the outcome scale. For each trial, we calculated the difference in effect size (i.e., standardized mean difference between nonblinded and blinded assessments). A difference in effect size of less than 0 suggested that nonblinded assessors generated more optimistic estimates of effect. We pooled the differences in effect size using inverse variance random-effects meta-analysis and used metaregression to identify potential reasons for variation. Results: We included 24 trials in our review. The main meta-analysis included 16 trials (involving 2854 patients) with subjective outcomes. The estimated treatment effect was more beneficial when based on nonblinded assessors (pooled difference in effect size −0.23 [95% confidence interval (CI) −0.40 to −0.06]). In relative terms, nonblinded assessors exaggerated the pooled effect size by 68% (95% CI 14% to 230%). Heterogeneity was moderate ( I 2 = 46%, p = 0.02) and unexplained by metaregression. Interpretation: We provide empirical evidence for Observer Bias in randomized clinical trials with subjective measurement scale outcomes. A failure to blind assessors of outcomes in such trials results in a high risk of substantial Bias.
Peter D Christenson - One of the best experts on this subject based on the ideXlab platform.
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the effect of investigator compliance Observer Bias on calculated efficacy in a pertussis vaccine trial
Pediatrics, 1998Co-Authors: J D Cherry, U Heininger, K Stehr, Peter D ChristensonAbstract:BACKGROUND: In the course of a large pertussis vaccine efficacy trial we realized that investigator compliance could have a major impact on calculated vaccine efficacy. DESIGN: In our pertussis vaccine efficacy trial, the study investigators were to monitor illness in study families by telephone every 2 weeks. If a cough illness of vaccine efficacy of an acellular pertussis component DTP vaccine (DTaP) and a whole cell pertussis component DTP vaccine (DTP) by compliance category. Bordetella pertussis infection was documented by culture of the organism in the study child or in a household contact or by a significant antibody response to pertussis toxin determined by enzyme-linked immunosorbent assay. RESULTS: Using a clinical case definition that included both mild and typical pertussis (cough illness vomiting (typical pertussis) the efficacy of DTaP vaccine was 69% (95% CI = 41-83) in the high compliance category and 86% (95% CI = 76-92) and 84% (95% CI = 64-93) in the intermediate and low compliance groups, respectively. In contrast, the efficacy of DTP vaccine did not vary by compliance category using this case definition. The attack rate in children vaccinated with diphtheria and tetanus toxoids vaccine (DT) was twofold less in low compliance physician practices when compared with the rates in high and intermediate groups. The DT/DTaP and DT/DTP fold-change differences were less in the high compliance group compared with the intermediate and low compliance groups. CONCLUSIONS: Our data suggest that Observer compliance (Observer Bias), can significantly inflate calculated vaccine efficacy. It is likely that all recently completed efficacy trials have been effected by this type of Observer Bias and all vaccines have considerably less efficacy against mild disease than published data suggest.
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The effect of investigator compliance (Observer Bias) on calculated efficacy in a pertussis vaccine trial.
Pediatrics, 1998Co-Authors: J D Cherry, U Heininger, K Stehr, Peter D ChristensonAbstract:BACKGROUND: In the course of a large pertussis vaccine efficacy trial we realized that investigator compliance could have a major impact on calculated vaccine efficacy. DESIGN: In our pertussis vaccine efficacy trial, the study investigators were to monitor illness in study families by telephone every 2 weeks. If a cough illness of
J D Cherry - One of the best experts on this subject based on the ideXlab platform.
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The effect of investigator compliance (Observer Bias) on calculated efficacy in a pertussis vaccine trial.
Pediatrics, 1998Co-Authors: J D Cherry, U Heininger, K Stehr, Peter D ChristensonAbstract:BACKGROUND: In the course of a large pertussis vaccine efficacy trial we realized that investigator compliance could have a major impact on calculated vaccine efficacy. DESIGN: In our pertussis vaccine efficacy trial, the study investigators were to monitor illness in study families by telephone every 2 weeks. If a cough illness of
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the effect of investigator compliance Observer Bias on calculated efficacy in a pertussis vaccine trial
Pediatrics, 1998Co-Authors: J D Cherry, U Heininger, K Stehr, Peter D ChristensonAbstract:BACKGROUND: In the course of a large pertussis vaccine efficacy trial we realized that investigator compliance could have a major impact on calculated vaccine efficacy. DESIGN: In our pertussis vaccine efficacy trial, the study investigators were to monitor illness in study families by telephone every 2 weeks. If a cough illness of vaccine efficacy of an acellular pertussis component DTP vaccine (DTaP) and a whole cell pertussis component DTP vaccine (DTP) by compliance category. Bordetella pertussis infection was documented by culture of the organism in the study child or in a household contact or by a significant antibody response to pertussis toxin determined by enzyme-linked immunosorbent assay. RESULTS: Using a clinical case definition that included both mild and typical pertussis (cough illness vomiting (typical pertussis) the efficacy of DTaP vaccine was 69% (95% CI = 41-83) in the high compliance category and 86% (95% CI = 76-92) and 84% (95% CI = 64-93) in the intermediate and low compliance groups, respectively. In contrast, the efficacy of DTP vaccine did not vary by compliance category using this case definition. The attack rate in children vaccinated with diphtheria and tetanus toxoids vaccine (DT) was twofold less in low compliance physician practices when compared with the rates in high and intermediate groups. The DT/DTaP and DT/DTP fold-change differences were less in the high compliance group compared with the intermediate and low compliance groups. CONCLUSIONS: Our data suggest that Observer compliance (Observer Bias), can significantly inflate calculated vaccine efficacy. It is likely that all recently completed efficacy trials have been effected by this type of Observer Bias and all vaccines have considerably less efficacy against mild disease than published data suggest.
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The effect of investigator compliance (Observer Bias) on calculated efficacy in a pertussis vaccine trial.
Pediatrics, 1998Co-Authors: J D Cherry, U Heininger, K Stehr, P ChristensonAbstract:In the course of a large pertussis vaccine efficacy trial we realized that investigator compliance could have a major impact on calculated vaccine efficacy. In our pertussis vaccine efficacy trial, the study investigators were to monitor illness in study families by telephone every 2 weeks. If a cough illness of >/=7 days duration was noted, the study child was to be evaluated. If the cough illness persisted for >/=14 days, the child was to be referred to a central investigator. For this report we analyzed study physician evaluation rates and rates of referral to the central investigators. Physician practices were separated into three compliance categories: high, intermediate, and low. We analyzed vaccine efficacy of an acellular pertussis component DTP vaccine (DTaP) and a whole cell pertussis component DTP vaccine (DTP) by compliance category. Bordetella pertussis infection was documented by culture of the organism in the study child or in a household contact or by a significant antibody response to pertussis toxin determined by enzyme-linked immunosorbent assay. Using a clinical case definition that included both mild and typical pertussis (cough illness >/=7 days duration) efficacy of DTaP vaccine was 40% (95% confidence interval [CI] = -3-65) in the high compliance category and 78% (95% CI = 65-86) and 75% (95% CI = 53-87) in the intermediate and low compliance groups, respectively. Similar, but less marked, differences in efficacy were noted with DTP vaccine recipients. Using a clinical case definition that required >/=21 days of cough with paroxysms, whoop, or vomiting (typical pertussis) the efficacy of DTaP vaccine was 69% (95% CI = 41-83) in the high compliance category and 86% (95% CI = 76-92) and 84% (95% CI = 64-93) in the intermediate and low compliance groups, respectively. In contrast, the efficacy of DTP vaccine did not vary by compliance category using this case definition. The attack rate in children vaccinated with diphtheria and tetanus toxoids vaccine (DT) was twofold less in low compliance physician practices when compared with the rates in high and intermediate groups. The DT/DTaP and DT/DTP fold-change differences were less in the high compliance group compared with the intermediate and low compliance groups. Our data suggest that Observer compliance (Observer Bias), can significantly inflate calculated vaccine efficacy. It is likely that all recently completed efficacy trials have been effected by this type of Observer Bias and all vaccines have considerably less efficacy against mild disease than published data suggest.
Asbjørn Hróbjartsson - One of the best experts on this subject based on the ideXlab platform.
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Observer Bias in randomized clinical trials with time to event outcomes systematic review of trials with both blinded and non blinded outcome assessors
International Journal of Epidemiology, 2014Co-Authors: Asbjørn Hróbjartsson, Ann Sofia Skou Thomsen, Frida Emanuelsson, Britta Tendal, Jeppe Vejlgaard Rasmussen, Jorgen Hilden, Isabelle Boutron, Philippe Ravaud, Stig BrorsonAbstract:Background: We wanted to evaluate the impact of nonblinded outcome assessors on estimated treatment effects in time-to-event trials. Methods: Systematic review of randomized clinical trials with both blinded and nonblinded assessors of the same time-to-event outcome. Two authors agreed on inclusion of trials and outcomes. We compared hazard ratios based on nonblinded and blinded assessments. A ratio of hazard ratios (RHR) <1 indicated that nonblinded assessors generated more optimistic effect estimates. We pooled RHRs with inverse variance randomeffects meta-analysis. Results: We included 18 trials. Eleven trials (1969 patients) with subjective outcomes provided hazard ratios, RHR 0.88 (0.69 to 1.12), (I 2 ¼44%, P ¼0.06), but unconditional pooling was problematic because of qualitative heterogeneity. Four atypical cytomegalovirus retinitis trials compared experimental oral administration with control intravenous administration of the same drug, resulting in Bias favouring the control intervention, RHR 1.33 (0.98 to 1.82). Seven trials of cytomegalovirus retinitis, tibial fracture and multiple sclerosis compared experimental interventions with standard control interventions, e.g. placebo, no-treatment or active control, resulting in Bias favouring the experimental intervention, RHR 0.73 (0.57 to 0.93), indicating an average exaggeration of nonblinded hazard ratios by 27% (7% to 43%). Conclusions: Lack of blinded outcome assessors in randomized trials with subjective time-to-event outcomes causes high risk of Observer Bias. Nonblinded outcome
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Lack of blinding of outcome assessors in animal model experiments implies risk of Observer Bias
Journal of Clinical Epidemiology, 2014Co-Authors: Segun Bello, Lasse T Krogsbøll, Jan Gruber, Zhizhuang Joe Zhao, Doris Fischer, Asbjørn HróbjartssonAbstract:Abstract Objectives To examine the impact of not blinding outcome assessors on estimates of intervention effects in animal experiments modeling human clinical conditions. Study Design and Setting We searched PubMed, Biosis, Google Scholar, and HighWire Press and included animal model experiments with both blinded and nonblinded outcome assessors. For each experiment, we calculated the ratio of odds ratios (ROR), that is, the odds ratio (OR) from nonblinded assessments relative to the corresponding OR from blinded assessments. We standardized the ORs according to the experimental hypothesis, such that an ROR Results We included 10 (2,450 animals) experiments in the main meta-analysis. Outcomes were subjective in most experiments. The pooled ROR was 0.41 (95% confidence interval [CI], 0.20, 0.82; I 2 = 75%; P Conclusion Lack of blinding of outcome assessors in animal model experiments with subjective outcomes implies a considerable risk of Observer Bias.
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Observer Bias in randomized clinical trials with measurement scale outcomes: a systematic review of trials with both blinded and nonblinded assessors
Canadian Medical Association Journal, 2013Co-Authors: Asbjørn Hróbjartsson, Ann Sofia Skou Thomsen, Frida Emanuelsson, Britta Tendal, Jorgen Hilden, Isabelle Boutron, Philippe Ravaud, Stig BrorsonAbstract:Background: Clinical trials are commonly done without blinded outcome assessors despite the risk of Bias. We wanted to evaluate the effect of nonblinded outcome assessment on estimated effects in randomized clinical trials with outcomes that involved subjective measurement scales. Methods: We conducted a systematic review of randomized clinical trials with both blinded and nonblinded assessment of the same measurement scale outcome. We searched PubMed, EMBASE, PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials, HighWire Press and Google Scholar for relevant studies. Two investigators agreed on the inclusion of trials and the outcome scale. For each trial, we calculated the difference in effect size (i.e., standardized mean difference between nonblinded and blinded assessments). A difference in effect size of less than 0 suggested that nonblinded assessors generated more optimistic estimates of effect. We pooled the differences in effect size using inverse variance random-effects meta-analysis and used metaregression to identify potential reasons for variation. Results: We included 24 trials in our review. The main meta-analysis included 16 trials (involving 2854 patients) with subjective outcomes. The estimated treatment effect was more beneficial when based on nonblinded assessors (pooled difference in effect size −0.23 [95% confidence interval (CI) −0.40 to −0.06]). In relative terms, nonblinded assessors exaggerated the pooled effect size by 68% (95% CI 14% to 230%). Heterogeneity was moderate ( I 2 = 46%, p = 0.02) and unexplained by metaregression. Interpretation: We provide empirical evidence for Observer Bias in randomized clinical trials with subjective measurement scale outcomes. A failure to blind assessors of outcomes in such trials results in a high risk of substantial Bias.
Lars Westerberg - One of the best experts on this subject based on the ideXlab platform.
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Observer Bias and random variation in vegetation monitoring data
Journal of Vegetation Science, 2008Co-Authors: Per Milberg, Johan Bergstedt, Jonas Fridman, Gunnar Odell, Lars WesterbergAbstract:Abstract Question: Detecting species presence in vegetation and making visual assessment of abundances involve a certain amount of skill, and therefore subjectivity. We evaluated the magnitude of the error in data, and its consequences for evaluating temporal trends. Location: Swedish forest vegetation. Methods: Vegetation data were collected independently by two Observers in 342 permanent 100-m2 plots in mature boreal forests. Each plot was visited by one Observer from a group of 36 and one of two quality assessment Observers. The cover class of 29 taxa was recorded, and presence/absence for an additional 50. Results: Overall, one third of each occurrence was missed by one of the two Observers, but with large differences among species. There were more missed occurrences at low abundances. Species occurring at low abundance when present tended to be frequently overlooked. Variance component analyses indicated that cover data on 5 of 17 species had a significant Observer Bias. Observer-explained variance was < 10% in 15 of 17 species. Conclusion: The substantial number of missed occurrences suggests poor power in detecting changes based on presence/absence data. The magnitude of Observer Bias in cover estimates was relatively small, compared with random error, and therefore potentially analytically tractable. Data in this monitoring system could be improved by a more structured working model during field work.
