Published evidence suggests that aspects of trial design lead to biased intervention effect estimates, but findings from different studies are inconsistent. This study combined data from 7 ...meta-epidemiologic studies and removed overlaps to derive a final data set of 234 unique meta-analyses containing 1973 trials. Outcome measures were classified as "mortality," "other objective," "or subjective," and Bayesian hierarchical models were used to estimate associations of trial characteristics with average bias and between-trial heterogeneity. Intervention effect estimates seemed to be exaggerated in trials with inadequate or unclear (vs. adequate) random-sequence generation (ratio of odds ratios, 0.89 95% credible interval {CrI}, 0.82 to 0.96) and with inadequate or unclear (vs. adequate) allocation concealment (ratio of odds ratios, 0.93 CrI, 0.87 to 0.99). Lack of or unclear double-blinding (vs. double-blinding) was associated with an average of 13% exaggeration of intervention effects (ratio of odds ratios, 0.87 CrI, 0.79 to 0.96), and between-trial heterogeneity was increased for such studies (SD increase in heterogeneity, 0.14 CrI, 0.02 to 0.30). For each characteristic, average bias and increases in between-trial heterogeneity were driven primarily by trials with subjective outcomes, with little evidence of bias in trials with objective and mortality outcomes. This study is limited by incomplete trial reporting, and findings may be confounded by other study design characteristics. Bias associated with study design characteristics may lead to exaggeration of intervention effect estimates and increases in between-trial heterogeneity in trials reporting subjectively assessed outcomes.
Randomized trials of adjunctive treatment of bacterial sepsis with polyclonal immunoglobulin show conflicting results. We performed a systematic review and a meta-analysis of the results of ...randomized trials that compared reductions in mortality rates in patient groups treated with polyclonal immunoglobulin versus either placebo or no treatment in addition to conventional treatment. High-quality trials had adequate concealment of allocation, were double-blinded and placebo-controlled, and made data available for intention-to-treat analyses. Twenty trials were included. Meta-analysis of all trials showed a relative risk of death with immunoglobulin treatment of 0.77 (95% confidence interval CI, 0.68-0.88). High-quality trials (involving a total of 763 patients, 255 of whom died) showed a relative risk of 1.02 (95% CI, 0.84-1.24), whereas other trials (involving a total of 948 patients, 292 of whom died) showed a relative risk of 0.61 (95% CI, 0.50-0.73). Because high-quality trials failed to demonstrate a reduction in mortality, polyclonal immunoglobulin should not be used for treatment of sepsis except in randomized clinical trials.
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Objectives To compare how allocation concealment is described in publications of randomised clinical trials and corresponding protocols, and to estimate how often trial publications with unclear ...allocation concealment have adequate concealment according to the protocol. Design Cohort study of 102 sets of trial protocols and corresponding publications. Setting Protocols of randomised trials approved by the scientific and ethical committees for Copenhagen and Frederiksberg, 1994 and 1995. Main outcome measures Frequency of adequate, unclear, and inadequate allocation concealment and sequence generation in trial publications compared with protocols, and the proportion of protocols where methods were reported to be adequate but descriptions were unclear in the trial publications. Results 96 of the 102 trials had unclear allocation concealment according to the trial publication. According to the protocols, 15 of these 96 trials had adequate allocation concealment (16%, 95% confidence interval 9% to 24%), 80 had unclear concealment (83%, 74% to 90%), and one had inadequate concealment. When retrospectively defined loose criteria for concealment were applied, 83 of the 102 trial publications had unclear concealment. According to their protocol, 33 of these 83 trials had adequate allocation concealment (40%, 29% to 51%), 49 had unclear concealment (59%, 48% to 70%), and one had inadequate concealment. Conclusions Most randomised clinical trials have unclear allocation concealment on the basis of the trial publication alone. Most of these trials also have unclear allocation concealment according to their protocol.
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BFBNIB, CMK, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Abstract Objective To compare the reporting on blinding in protocols and articles describing randomized controlled trials. Study Design and Setting We studied 73 protocols of trials approved by the ...scientific/ethical committees for Copenhagen and Frederiksberg, 1994 and 1995, and their corresponding publications. Results Three out of 73 trials (4%) reported blinding in the protocol that contradicted that in the publication (e.g., “open” vs. “double blind”). The proportion of “double-blind” trials with a clear description of the blinding of participants increased from 11 out of 58 (19%) when based on publications alone to 39 (67%) when adding the information in the protocol. The similar proportions for the blinding of health care providers were 2 (3%) and 22 (38%); and for the blinding of data collectors, they were 8 (14%) and 14 (24%). In 52 of 58 publications (90%), it was unclear whether all patients, health care providers, and data collectors had been blinded. In 4 of the 52 trials (7%), the protocols clarified that all three key trial persons had been blinded. Conclusions The reporting on blinding in both trial protocols and publications is often inadequate. We suggest developing international guidelines for the reporting of trial protocols and public access to protocols.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Aims To explore whether the coding region of the islet amyloid polypeptide (IAPP) gene contains genetic variants associated with Type 2 diabetes and whether a previously reported association of the ...promoter variant −132g→a with Type 2 diabetes could be reproduced in Danish Caucasians.
Methods The coding region was analyzed using single strand conformation polymorphism (SSCP) and heteroduplex analysis in 192 Type 2 diabetic patients. Restriction fragment length polymorphism (RFLP) was employed to screen for the promoter variant in 414 Type 2 diabetic patients and 182 glucose‐tolerant control subjects.
Results The SSCP analysis identified an IVS+75a→g variant in two patients. The frequency of heterozygous carriers of the promoter variant in the case–control study was 4.1% (17/414) and 7.1% (13/182), respectively. Odds ratio of the prevalence of Type 2 diabetes in carriers compared with non‐carriers was estimated to be 0.47 (95% confidence interval 0.19, 1.15).
Conclusion Neither variability in the coding region of the IAPP gene nor the −132g→a promoter variant was associated with Type 2 diabetes among the studied Danish Caucasians.
Diabet. Med. 20, 491–494 (2003)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Systemic and local allergy to human insulin Wittrup, Minna; Pildal, Julie; Rasmussen, Ase Krogh ...
Ugeskrift for læger,
2003-May-19, Volume:
165, Issue:
21
Journal Article
After introduction of recombinant human insulin, immunological reactions have become rare, but symptomatic immune reactions to insulin still occur. We present four insulin-treated diabetic patients ...who developed hypersensitivity to insulin or additives to insulin preparations. We show that symptomatic immunological reactions to insulin have not been eliminated by the introduction of recombinant human insulin. Furthermore it demonstrates the importance of skin-biopsy-verified diagnoses and the relevance of differentiation between different types of insulin allergy.
Somatostatin (SRIF) is a widely distributed regulatory peptide. Recently, it was shown that human seminal plasma contains high concentrations of SRIF. In order to find the cellular source of seminal ...SRIF we have examined the presence of SRIF in porcine urogenital tissues. The concentration of SRIF in male accessory reproductive tissues of 3-month-old pigs (N = 4) ranged from 1 to 17 nmol/kg. In the boar, only the prostate gland contained significant amounts of SRIF (median 7 nmol/kg, range 3-18 nmol/kg, N = 4). Testis and semen contained no SRIF. Gel chromatography of extracts of the male accessory sex glands and epididymis showed both SRIF-28 and SRIF-14, whereas urinary bladder contained mainly SRIF-14. In conclusion, the results show a considerable species, tissue and developmental variation in the expression of SRIF in the genitourinary tract.
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