A review of blinding in randomized controlled trials found results inconsistent and questionable

BACKGROUND AND OBJECTIVE: To determine methods to assess the success of blinding in randomized controlled trials (RCTs). METHODS: We searched MEDLINE, the Cochrane Controlled Trials Register, and the Cochrane Method Register and performed a manual search to target studies that attempt to assess blinding and describe the methods used in those studies. RESULTS: A total of 90 reports were selected. Reports assessed the success of blinding participants (n = 58), care providers (n = 36), and outcome assessors (n = 15). Of the 58 reports assessing the success of blinding participants, 54 (93%) reported asking participants to guess their treatment assignment. There was no consistency in timing of assessment (e.g., once at the end of the trial, 57%, or several times during the trial, 26%) or modalities of answering (e.g., "do not know" answers, 43%, or participants forced to guess, 31%). A statistical analysis was performed in 57% of reports. The statistical analysis mainly compared the proportion of correct guesses to those produced by chance (32%) or checked for a relation between participants' guesses and treatment assignment (23%). CONCLUSIONS: Methods of assessing the success of blinding, analysis and reporting the results were inconsistent and questionable.     

The deleterious G15498A mutation in mitochondrial DNA-encoded cytochrome b may remain clinically silent in homoplasmic carriers

We report on a patient with severe growth retardation and IgF1 deficiency, in which a mitochondrial abnormality was suspected. An isolated mitochondrial respiratory chain complex III deficiency was found in blood lymphocytes and skin fibroblasts. Sequence analysis of the cytochrome b, which is the only mitochondrial DNA-encoded subunit of complex III, revealed a homoplasmic G15498A mutation, resulting in the substitution of a highly conserved amino acid (glycine 251 into an aspartic acid). The mutation was found to be homoplasmic in all tissues examined from the mother and her brother (lymphocytes, fibroblasts, hair roots and buccal cells). Complex III deficiency was also demonstrated in these cells. Nevertheless, the mother and the brother were asymptomatic. This mutation had been considered as a cardiomyopathy-generating mutation in a previously reported case, and its pathogenicity has been demonstrated recently in yeast. However, it seems not to fulfil the classical criteria for pathogenicity of a mitochondrial DNA mutation, especially the heteroplasmic status, and to be clinically silent, albeit present, in nonaffected relatives. We suggest that other factors are contributing to the clinical variability expression of the G15498A mtDNA mutation.     

Methodological differences in clinical trials evaluating nonpharmacological and pharmacological treatments of hip and knee osteoarthritis

Context  Randomized controlled trials have been developed essentially in the context of pharmacological treatments (ie, oral drugs; intra-articular injection; and topical, intramuscular, and intravenous treatments), but assessment of the effectiveness of nonpharmacological treatments (ie, surgery, arthroscopy, joint lavage, rehabilitation, acupuncture, and education) presents specific issues. Objectives  To compare the quality of articles of nonpharmacological and pharmacological treatments of hip and knee osteoarthritis and to identify specific methodological issues related to assessment of nonpharmacological treatments. Design and Setting  We searched MEDLINE and the Cochrane Central Register of Controlled Trials for articles of randomized controlled trials published between January 1, 1992, and February 28, 2002, in 28 general medical and specialty journals with high impact factors and assessing nonpharmacological and pharmacological treatments in patients with hip or knee osteoarthritis. Main Outcome Measures  The quality of the methods reported in the selected articles was assessed by 2 independent reviewers using the Jadad scale, the Delphi list, and guidelines found in the Users' Guides to the Medical Literature. Investigators also used a checklist of items developed by the authors to analyze study characteristics. Results  A total of 110 articles were included in the analysis; 50 (45.5%) assessed nonpharmacological treatments and 60 (54.5%) assessed pharmacological treatments. Reports of nonpharmacological treatments had a lower global quality score than did reports of pharmacological treatments as measured by the Jadad scale (mean [SD] score, 1.4 [1.3] vs 3.0 [1.3]) and the Delphi list (mean [SD] score, 5.2 [1.5] vs 7.5 [1.1]). Lack of reporting adequate random sequence generation and intention-to-treat analyses were found in both nonpharmacological and pharmacological articles. Nonpharmacological treatments were less often compared with a placebo than were pharmacological treatments (28.0% of articles vs 71.7%). Compared with pharmacological articles, nonpharmacological articles less often described blinding of patients (26.0% vs 96.7%), care providers (6.0% vs 81.7%), and outcome assessors (68.0% vs 98.3%). Care providers' skill levels could influence treatment effect in 84.0% of nonpharmacological articles vs 23.3% of pharmacological articles. Conclusions  In this analysis of reports of hip and knee osteoarthritis therapy, nonpharmacological articles scored lower than pharmacological articles in terms of quality. Assessments of nonpharmacological treatments must take into consideration additional methodological issues.      

Cancer of the esophagus in the department of C?te-d'Or

The registry of digestive tract tumors established for the department of C?te-d' Or was used to study the incidence and characteristics of oesophageal cancer in the area. The crude annual incidence rate was 15.5/100,000 for males, ans 1.1/100,000 for females. The corresponding age standardized rate (world standard) were 12.7 and 0.6. The sex ratio was 21.2. As compared to other cancer registries the C?te-d' Or is in intermediate range for males, in the low range for females. The incidence of oesophageal cancer was similar in urban and rural areas. The risk of oesophageal cancer in males was five times higher in workers than in high executives and professionals. There was no significant variation in oesophageal cancer incidence over the 8 years of the study. Rates tended to decrease slightly in both sexes. Most cancers were squamous cell carcinomas (92%). Adenocarcinomas represented 5% of the cases. The risk of an associated tumour of the upper respiratory and digestive tract was important (17.5%). Only 10.4% of the patients underwent curative surgery, while 53.4% were referred for radiotherapy alone. The overall 1-year survival rate was 18.4%, and the 5-year survival rate was 2.8%. The 5-year survival rate was 7.2% after curative surgery, and 3.2% after radiotherapy. These results underline the fact that the prognosis of oesophageal cancer in a well defined population where only one patient out of ten can benefit from curative surgery, remains poor.     

Quality of reporting internal and external validity data from randomized controlled trials evaluating stents for percutaneous coronary intervention

Background  

Stents are commonly used to treat patients with coronary artery disease. However, the quality of reporting internal and external validity data in published reports of randomised controlled trials (RCTs) of stents has never been assessed.     

报告非药物随机对照临床试验的CONSORT扩展声明：说明与详述（一）

正确报告随机对照临床试验（randomized controlled trial,RCT）是严格评价试验结果真实性与有效性的必要前提。含22项条目清单和流程图的CONSORT（Consolidated Standards of Reporting Trials）声明旨在通过改进RCT的报告来解决这一问题。然而,《CONSORT声明》中没有专门论及那些适用于非药物治疗（如手术、技术干预、仪器设备、康复理疗、心理治疗和行为干预等）临床试验的具体问题。此外,相当多的证据表明非药物临床试验的报告仍然需要改进,因此CONSORT小组针对评估非药物治疗的临床INFORMATION FOR AUTHORS试验制定了《CONSORT扩展声明》。为制定《CONSORT扩展声明》以规范非药物临床试验的报告,33名专家于2006年2月在法国巴黎组织召开了讨论会议,并就此达成了共识。与会者扩充了原有《CONSORT声明》中的11项条目,新增了1项条目,修改并重新制定了报告流程图。 为便于充分理解和执行《CONSORT扩展声明》,CONSORT小组通过对文献的回顾编制了这一说明与详述文本,旨在为正确报告非药物临床试验提供范例。本扩展声明,连同《CONSORT声明》以及《CONSORT声明》的其他扩展本,将有助于改进非药物治疗领域RCT的报告。