scholarly journals Combining Survival and Toxicity Effect Sizes from Clinical Trials: NCCTG 89-20-52 (Alliance)

2018 ◽  
Vol 7 (4) ◽  
pp. 137-146
Author(s):  
Brittny T. Major- Elechi ◽  
Paul J. Novotny ◽  
Jasvinder A. Singh ◽  
James A. Bonner ◽  
Amylou C. Dueck ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Effect Sizes ◽  
Toxicity Effect

scholarly journals Comparative clinical trials in psychotherapy: Have large effects been replicated?

2020 ◽  
Vol 29 ◽  
Author(s):  
Nickolas D. Frost ◽  
Thomas W. Baskin ◽  
Bruce E. Wampold
Keyword(s):  
Clinical Trials ◽  
Treatment Efficacy ◽  
Literature Search ◽  
Meta Analysis ◽  
Effect Sizes ◽  
Depression And Anxiety ◽  
Inclusion Criteria ◽  
Average Quality ◽  
Meta Analyses

Abstract Aims The purpose of this review is to examine the replication attempts of psychotherapy clinical trials for depression and anxiety. We focus specifically on replications of trials that exhibit large differences between psychotherapies. The replicability of these trials is especially important for meta-analysis, where the inclusion of false-positive trials can lead to erroneous conclusions about treatment efficacy. Methods Standard replication criteria were developed to distinguish direct from conceptual replication methodologies. Next, an exhaustive literature search was conducted for published meta-analyses of psychotherapy comparisons. Trials that exhibited large effects (d > 0.8) were culled from these meta-analyses. For each trial, a cited replication was conducted to determine if the trial had been subsequently replicated by either ‘direct’ or ‘conceptual’ methods. Finally, a broader search was conducted to examine the extent of replication efforts in the psychotherapy literature overall. Results In the meta-analytic search, a total of N = 10 meta-analyses met the inclusion criteria. From these meta-analyses, N = 12 distinct trials exhibited large effect sizes. The meta-analyses containing more than two large effect trials reported evidence for treatment superiority. A cited replication search yielded no direct replication attempts (N = 0) for the trials with large effects, and N = 4 conceptual replication attempts of average or above average quality. However, of these four attempts, only two partially corroborated the results from their original trial. Conclusion Meta-analytic reviews are influenced by trials with large effects, and it is not uncommon for these reviews to contain several such trials. Since we find no evidence that trials with such large effects are directly replicable, treatment superiority conclusions from these reviews are highly questionable. To enhance the quality of clinical science, the development of authoritative replication criteria for clinical trials is needed. Moreover, quality benchmarks should be considered before trials are included in a meta-analysis, or replications are attempted.

Proposals for Sample Size Calculation Programs

2007 ◽  
Vol 46 (06) ◽  
pp. 655-661 ◽  
Author(s):  
H. Heinzl ◽  
A. Benner ◽  
C. Ittrich ◽  
M. Mittlböck
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Sample Size ◽  
Sample Size Calculation ◽  
Effect Sizes ◽  
Detectable Effect ◽  
Planning Stage ◽  
Type Iii ◽  
Error Risk ◽  
Q Values

Summary Objectives : Numerous sample size calculation programs are available nowadays. They include both commercial products as well as public domain and open source applications. We propose modifications for these programs in order to even better support statistical consultation during the planning stage of a two-armed clinical trial. Methods : Directional two-sided tests are commonly used for two-armed clinical trials. This may lead to a non-negligible Type III error risk in a severely underpowered study. In the case of a reasonably sized study the question for the so-called auxiliary alternative may evolve. Results : We propose that sample size calculation programs should be able to compute i) Type III errors and the so-called (q-values, ii) minimum sample sizes required to keep the (q-values below pre-specified levels, and iii) detectable effect sizes of the so-called auxiliary alternatives. Conclusions : Proposals iand ii are intended to help prevent irresponsibly underpowered clinical trials, whereas the proposal iii is meant as additional assistance for the planning of reasonably sized clinical trials.

scholarly journals Exploratory analysis of comparative clinical trials used for marketing approval in patients with type 2 diabetes in Japan

2019 ◽  
Vol 7 ◽  
pp. 205031211882340 ◽  
Author(s):  
Reina Kaneko ◽  
Shunsuke Ono
Keyword(s):  
Clinical Trials ◽  
Combination Therapy ◽  
Treatment Guideline ◽  
Lower Proportion ◽  
New Drugs ◽  
Effect Sizes ◽  
Marketing Approval ◽  
Phase 2 ◽  
Baseline Hba1c ◽  
Male Subjects

Background/objectives: The results of phase 2 and 3 clinical trials, which justify decisions regarding marketing approval for new drugs, are used for comparison of drugs in the post-marketing phase. A number of meta-analyses of approved antidiabetics have been performed, but the heterogeneity of trials has not been fully examined. The aim of this study was to explore factors that may influence baseline HbA1c in trial samples and treatment outcomes (i.e. HbA1c reductions and effect sizes), with the goal of providing unbiased and fair retrospective comparisons between different antidiabetics. Method: We conducted three meta-regression analyses using 78 randomized or non-randomized comparative phase 2 or 3 trials of 24 approved antidiabetics in Japan, conducted from 1987 to 2012. Results: Baseline HbA1c of each arm was higher in phase 2 trials, trials with a greater number of subjects, trials with a lower proportion of male subjects, trials of combination therapy, or trials with longer subject disease duration. Entry criteria were different among drug classes and caused variations in baseline HbA1c. HbA1c reductions were larger in non-randomized trials, trials with a shorter treatment period, or trials with a lower proportion of male subjects. Effect sizes were larger in phase 2 trials, or trials of combination therapy. Larger effect sizes were observed in drugs with later market entry for alpha-glucosidase inhibitors and glinides. Conclusion: Baseline HbA1c, an important characteristic of subjects enrolled in trials of antidiabetics, differed significantly across trials. Differences in features of study subjects were caused by explicit stipulations in eligibility criteria of HbA1c and also by other conditions (e.g. trial design, regulatory guidance, treatment guideline) and/or interventions of investigators and pharmaceutical companies that were specific to drugs and trials. Healthcare professionals should carefully consider these heterogeneities in trials used for marketing approval review when making a retrospective comparison to select the best treatment option for patients.

Problems with the MetaBLIND study: An examination of data on blinding patients in trials with patient-reported outcomes

2021 ◽  
pp. 135910532110593
Author(s):  
Michiel Tack
Keyword(s):  
Clinical Trials ◽  
Epidemiological Study ◽  
Study Design ◽  
Patient Reported Outcomes ◽  
Randomized Trials ◽  
Effect Sizes ◽  
Patient Reported ◽  
The Impact ◽  
Trial Participants

MetaBLIND is the largest meta-epidemiological study on the impact of blinding in randomized trials to date. We examined MetaBLIND data on the impact of blinding patients on patient-reported outcomes. 68 out of 132 included trials tested knowledge recall and had questionable relevance to clinical trials. In 17 out of 18 comparisons, the number of trials in the blinded or nonblinded group was 2 or lower. In several key trials, the blinding status was uncertain. Effect sizes compared in MetaBLIND appear to reflect random differences in study design and setting rather than the impact of blinding trial participants.

scholarly journals Still cooling after all these years: Meta-analysis of pre-clinical trials of therapeutic hypothermia for acute ischemic stroke

2016 ◽  
Vol 36 (7) ◽  
pp. 1157-1164 ◽  
Author(s):  
Oana M Dumitrascu ◽  
Jessica Lamb ◽  
Patrick D Lyden
Keyword(s):  
Clinical Trials ◽  
Ischemic Stroke ◽  
Therapeutic Hypothermia ◽  
Meta Analysis ◽  
Considerable Improvement ◽  
Effect Sizes ◽  
Preclinical Studies ◽  
The Past ◽  
Further Development ◽  
Experimental Cerebral Ischemia

Therapeutic hypothermia is the most potent neuroprotectant for experimental cerebral ischemia, illustrated in a 2007 meta-analysis published in this journal. To address recent therapeutic nihilism, we systematically reviewed recent experimental literature. Quality scoring showed considerable improvement in study design. Using several outcome measures in a variety of models and species, therapeutic hypothermia was protective compared with normothermia, with powerful and statistically significant normalized treatment effect sizes, in 60 papers comprising 216 comparisons. In the past 5 years, preclinical studies of ischemic stroke re-emphasize that therapeutic hypothermia is potently effective, justifying further development in larger human clinical trials.

scholarly journals Certainty of genuine treatment increases drug responses among intellectually disabled patients

Neurology ◽  
2017 ◽  
Vol 88 (20) ◽  
pp. 1912-1918 ◽  
Author(s):  
Karin B. Jensen ◽  
Irving Kirsch ◽  
Moa Pontén ◽  
Annelie Rosén ◽  
Kathy Yang ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Fragile X ◽  
Meta Analysis ◽  
Effect Sizes ◽  
Controlled Trials ◽  
Trial Duration ◽  
Open Label ◽  
Drug Responses ◽  
Treatment Responses ◽  
Pharmacologic Treatments

Objective:To determine the placebo component of treatment responses in patients with intellectual disability (ID).Methods:A statistical meta-analysis comparing bias-corrected effect sizes (Hedges g) of drug responses in open-label vs placebo-controlled clinical trials was performed, as these trial types represent different certainty of receiving genuine treatment (100% vs 50%). Studies in fragile X, Down, Prader-Willi, and Williams syndrome published before June 2015 were considered.Results:Seventeen open-label trials (n = 261, 65% male; mean age 23.6 years; mean trial duration 38 weeks) and 22 placebo-controlled trials (n = 721, 62% male; mean age 17.1 years; mean trial duration 35 weeks) were included. The overall effect size from pre to post treatment in open-label studies was g = 0.602 (p = 0.001). The effect of trial type was statistically significant (p = 0.001), and revealed higher effect sizes in studies with 100% likelihood of getting active drug, compared to both the drug and placebo arm of placebo-controlled trials. We thus provide evidence for genuine placebo effects, not explainable by natural history or regression toward the mean, among patients with ID.Conclusions:Our data suggest that clinical trials in patients with severe cognitive deficits are influenced by the certainty of receiving genuine medication, and open-label design should thus not be used to evaluate the effect of pharmacologic treatments in ID, as the results will be biased by an enhanced placebo component.

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