Quality of reporting of randomization methodology in nephrology trials
Authors: Steven Fishbane, Azzour D. Hazzan, Shayan Shirazian, Ezra Israel, Giovanni F. Strippoli
Journal: Kidney International (2012)

The randomized controlled trial (RCT) is the ideal study design to address intervention questions.1.Green S.B. Byar D.P. Using observational data from registries to compare treatments: the fallacy of omnimetrics.Stat Med. 1984; 3: 361-373Crossref PubMed Scopus (126) Google Scholar In an RCT, patients are allocated to an intervention or control group on the basis of chance. The strengths of this methodology include that it minimizes confounding by producing groups that are comparable in terms of baseline characteristics. In theory, this provides comparable prognoses of the groups prior to intervention. The reliability of an individual RCT, however, is affected by the methodological aspects of randomization procedures, which are reflected by the completeness and quality of reporting. When reporting is inadequate or superficial, confidence in the credibility of study procedures and results is diminished. There are certain attributes that define the quality of the procedures and reporting of RCTs. The Consolidated Standards of Reporting Trials (CONSORT) Statement, a widely accepted set of standards for reporting of clinical trials, lists four minimum requirements for reporting of randomization methodology.2.The CONSORT Statement CONSORT: Transparent Reporting of Trials.http://www.consort-statement.org/consort-statement/Date: 2012Google Scholar The first is a clear explanation of the method by which the random sequence is generated. Second is an explanation of the type of randomization as simple randomization, permuted block (to avoid imbalances in allocation), stratification (to balance the distribution of certain baseline risk factors), or a combination of these techniques. Third is allocation concealment, the method of preventing study personnel from having awareness of treatment assignment before enrolling patients. Finally, there needs to be full reporting on the methods of implementation of randomization procedures.2.The CONSORT Statement CONSORT: Transparent Reporting of Trials.http://www.consort-statement.org/consort-statement/Date: 2012Google Scholar It is well worth noting that the CONSORT Statement goes well beyond reporting on randomization, and other aspects are highly valuable.2.The CONSORT Statement CONSORT: Transparent Reporting of Trials.http://www.consort-statement.org/consort-statement/Date: 2012Google Scholar Clinicians, guideline groups, and policy makers rely on the results of RCTs. It is clear, therefore, that the quality of design, conduct, and reporting of RCTs is a fundamental step in determining valid and applicable results. Studies with suboptimal quality may be misleading as to the true effects of interventions. The ability to advance clinical care may hence be hindered, while both resources and the volunteerism of study subjects may be squandered. High-quality reporting of methodology increases the credibility, applicability, and generalizability of methods and results. It should be noted that nephrology publishes the fewest RCTs of any medical specialty.3.Strippoli G.F. Craig J.C. Schena F.P. The number, quality, and coverage of randomized controlled trials in nephrology.J Am Soc Nephrol. 2004; 15 (accessed 10 January 2012): 411-419Crossref PubMed Scopus (269) Google Scholar When the number of RCTs in a field is less, then the contribution of each individual study to the accumulated literature and knowledge base is proportionately greater. As a result there is an even heightened burden of responsibility for high-quality reporting. The purpose of this Editorial is to discuss quality of randomization reporting in clinical trials in nephrology. We reviewed nephrology RCTs published in 13 nephrology and four general medical journals between 1 July 2010 and 30 June 2011 (see Supplementary Methods and Supplementary Figure S1 online) to explore these domains. A total of 74 articles met the inclusion criteria, and their characteristics are reported in Table 1. Sixty of 74 (82%) were published in nephrology journals, and 52 of 74 (70%) had sample sizes of fewer than 200 patients.Table 1Characteristics of randomized controlled trials analyzed The four CONSORT indicators of the quality of randomization could be ascertained from all articles. The method of sequence generation was not reported in 44 of 74 studies (59.5%) (Table 2). Randomization type was not reported in 29 of 74 publications (39.2%). When the type was reported, some form of stratification, permuted block, or a combination was used in 48.6% of studies (permuted block alone in 12.2%, stratification alone in 20.3%). Most studies that did not report randomization type used simple randomization, on the basis of responses provided by the authors of 16 studies. The method of allocation concealment was not reported in 43 of 74 studies (58.1%); when it was reported, central allocation was the most common procedure. Finally, in the vast majority of cases, information was not provided on how and by whom randomization was implemented.Table 2Randomization characteristics Only 5 of 74 studies (6.8%) reported sufficiently on all four items identified in the CONSORT Statement. Importantly, 19 of 74 articles (25.7%) provided no information at all on randomization methodology. For what are arguably the two most critical aspects of randomization reporting, randomization type and method of allocation concealment, only 24 of 74 studies (32.4%) reported acceptably. We analyzed these 24 publications to explore how they differed from other published studies and which were the factors predictive of acceptable reporting. Single-center studies were less likely than multicenter studies to report adequately on the key components (15.2% versus 46.3%, P = 0.006), and studies with binary and time-to-event primary end points were more likely than studies that used continuous primary end points (55.6% versus 19.1%, P = 0.002). It should be noted that these are associations and not necessarily inherent causes of reporting deficiencies. There was a larger effect size for the primary end point in studies with inadequate reporting of randomization; studies with acceptable reporting found smaller effect sizes (0.16±0.09 versus 0.34±0.16, P < 0.001). This is confirmatory of the possibility raised by others that as methodological quality falls, reported intervention effect size increases.4.Schulz K.F. Chalmers I. Hayes R.J. Altman D.G. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials.JAMA. 1995; 273: 408-412Crossref PubMed Scopus (3989) Google Scholar Taken together, our findings indicate that reporting of randomization methodology is suboptimal in most nephrology trial publications. Because our analysis was not comprehensive, but limited to major and second-line journals, a degree of selection bias may possibly be a limitation. Previously, it has been reported that nephrology lags behind all other medical specialties in the number of published RCTs.3.Strippoli G.F. Craig J.C. Schena F.P. The number, quality, and coverage of randomized controlled trials in nephrology.J Am Soc Nephrol. 2004; 15 (accessed 10 January 2012): 411-419Crossref PubMed Scopus (269) Google Scholar Although the number increased between 1966 and 2010, nephrology still publishes the fewest RCTs.5.Palmer S.C. Sciancalepore M. Strippoli G.F. Trial quality in nephrology: how are we measuring up?.Am J Kidney Dis. 2011; 58: 335-337Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar It is worth noting that the problem of low quality of reporting on randomization procedures has been found in other specialties as well.6.Gravel J. Opatrny L. Shapiro S. The intention-to-treat approach in randomized controlled trials: are authors saying what they do and doing what they say?.Clin Trials. 2007; 4: 350-356Crossref PubMed Scopus (102) Google Scholar,7.Baron G. Boutron I. Giraudeau B. Ravaud P. Violation of the intent-to-treat principle and rate of missing data in superiority trials assessing structural outcomes in rheumatic diseases.Arthritis Rheum. 2005; 52: 1858-1865Crossref PubMed Scopus (44) Google Scholar Clear and thorough reporting is essential for understanding the rigor of randomization processes. A failure to report on key aspects of randomization methodology diminishes the credibility of reported results, and this is particularly important in disciplines such as nephrology, where there are few randomized trials to reliably inform practice. Accordingly, the CONSORT Statement places particular emphasis on reporting requirements related to randomization in publications.2.The CONSORT Statement CONSORT: Transparent Reporting of Trials.http://www.consort-statement.org/consort-statement/Date: 2012Google Scholar Adequate description of the method used to generate the random allocation sequence makes it possible to assess the likelihood of bias in the process. The type of randomization needs to be described so that the reader can assess whether any restrictions were in place, and how they were employed. It is acceptable to state, “The method of patient allocation was simple randomization,” if this was the method. In contrast, if block randomization was used, then the method for block generation and block size should be specified. For stratification, which variables were involved and cutoff values within strata should be delineated. The method of allocation concealment should be clearly explained to assure that investigators were blinded to new patients’ treatment assignment. Acceptable methods are allocation by a central source, use of a pharmacy independent of study-blinded personnel, and use of sequentially numbered opaque sealed envelopes. Finally, the methods of randomization implementation help the reader understand who generated the randomization sequence, enrolled participants, and assigned patients to interventions. Altogether, rigorous reporting creates confidence in the credibility of study procedures and results. However, as important as reporting quality is, the design and execution of the randomization process are vitally important as well. It is not always possible from the published article to ascertain these characteristics of a study. In conclusion, we found that reporting of randomization methodology was insufficient in the majority of published nephrology RCTs. Because of the effort and resources devoted to RCTs, it is important that the results can be relied upon. When reporting is insufficient, the applicability and reliability of results are weaker, and the evidentiary value of the results is diminished. We recommend that investigators in nephrology design RCTs and report results following the CONSORT Statement criteria, and that editors of journals pay particular attention to adequate reporting of the randomization processes. Supplementary Methods. Figure S1. Articles selected for analysis. Corrections to "For the article ‘Quality of reporting of randomization methodology in nephrology trials’"Kidney InternationalVol. 83Issue 5PreviewCorrection to: Kidney International (2012) 82, 1144–1146. doi:10.1038/ki.2012.335 Full-Text PDF Open Archive