Prospective Trial Registration Research Articles

Prospective Trial Registration for Clinical Research

Optimizing evidence-based medicine--and therefore the care of our patients--requires a public record of both the benefits and the risks of various medical interventions. Unfortunately, available evidence is often skewed because some clinical trials are withheld from publication; only selected data are reported, and statistical techniques are often inappropriately determined following data analysis. Prospective clinical trial registration (PCTR) is the public documentation of trial protocols--today primarily on the Internet--before data analysis (and ideally before trial commencement). The primary goals of PCTR are to reduce selective reporting and improve data analysis transparency, but it may also promote trial awareness for the public and other investigators. Prospective clinical trial registration is certainly not without problems, but many have been resolved, and the remainder is relatively minor in nature and easily overcome. Multiple organizations endorse (in some cases mandate) PCTR, including prominent committees of medical editors, the World Health Organization, the World Medical Association (responsible for the Helsinki Declaration), and, more recently, the US Food and Drug Administration. Although Regional Anesthesia and Pain Medicine does not currently require registration for published articles, PCTR in this and other anesthesiology and pain journals may become mandatory within the next few years. Potential authors/investigators will therefore benefit from becoming familiar with PCTR before mandatory registration implementation, and familiarity among readers may improve interpretation and understanding of clinical research results.

Australian New Zealand Clinical Trials Registry: history and growth

The problem of publication bias and the need for prospective trial registration to overcome this issue has been recognised for many years. Australia and New Zealand established a national clinical trials registry, the Australian New Zealand Clinical Trials Registry (ANZCTR, http://www.anzctr.org.au), in 2005. Much progress has been made over the past six years on this important research infrastructure resource, with the ANZCTR now housing over 5330 registered trial records. Recent reviews and initiatives have helped encourage prospective registration of Australian/New Zealand trials but several challenges remain. We continue to work to ensure all those interested in clinical trials being conducted in Australia and New Zealand (including consumers, clinicians, researchers, funders and regulators) are able to access information that is comprehensive, complete, current and compatible.

Developing a geographic search filter to identify randomised controlled trials in Africa: finding the optimal balance between sensitivity and precision

Research on identifying trials using geographic filters is limited. To test the sensitivity and precision of a filter to identify African randomised controlled trials (RCTs). We searched medline and embase for RCTs published in 2004 using a Cochrane filter for RCTs. The search was limited to HIV/AIDS but irrespective of location. Two investigators independently identified African RCTs from the retrieved records forming a reference set. We then repeated the search using an African geographic filter comprising country and regional terms forming the filter set. We compared the sensitivity and precision of the sets. The medline reference set comprised 1799 records with 23 African RCTs; for embase, the reference set comprised 763 records with 37 African RCTs. The medline filter set comprised 180 records with 17 African RCTs; the embase filter set comprised 98 records with 27 African RCTs. Sensitivity of the filter was 74% (medline) and 73% (embase). Addition of the filter improved precision from 1.3% to 9.4% (medline) and from 5% to 28% (embase). The African filter improved precision with some loss in sensitivity. Incomplete reporting of trial location in electronic bibliographic records restricts efficiency of geographic filters. Prospective trial registration should alleviate this.

Problems in the reporting of acne clinical trials: a spot check from the 2009 Annual Evidence Update on Acne Vulgaris.

In the course of producing the 2009 NHS Evidence - skin disorders Annual Evidence Update on Acne Vulgaris, 25 randomised controlled trials were examined. From these, at least 12 potentially serious problems of trial reporting were identified. Several trials concluded no effect of a treatment yet they were insufficiently powered to exclude potentially useful benefits. There were examples of duplicate publication and "salami publication", as well as two trials being combined and reported as one. In some cases, an incorrect "within-groups" statistical comparison was made and one trial report omitted original efficacy data and included only P values. Both of the non-inferiority studies examined failed to pre-specify a non-inferiority margin. Trials reported as "double-blind" compared treatments that were dissimilar in appearance or had differing adverse effect profiles. In one case an intention-to-treat analysis was not performed and there was a failure to account for all of the randomized participants. Trial results were made to sound more impressive by selective outcome reporting, emphasizing the statistical significance of treatment effects that were clinically insignificant, and by the use of larger-sounding odds ratios rather than rate ratios for common events. Most of the reporting problems could have been avoided by use of the CONSORT guidelines and prospective trial registration on a public clinical trials database.

Reporting bias and other biases affecting systematic reviews and meta-analyses: a methodological commentary

Systematic reviews and meta-analyses often occupy the top of the hierarchy of evidence in support of evidence-based clinical practice. These studies commonly inform the formulation of clinical guidelines. Bias can intrude at several levels during the conduct of systematic reviews. The effect these various biases, in particular reporting bias, have on pooled estimates and review inferences are potentially significant. In this review, we describe several forms of selection and reporting biases that may occur during the conduct of a systematic review, how these biases might affect a review and what steps could help minimize their influence on review inferences. Specifically, we support calls for prospective international trial registration and open access to trial protocols as two potential solutions that may improve the methodological quality of systematic reviews and the validity of their results.

Evidence of publication bias in reporting acute stroke clinical trials

To ascertain the extent of publication bias in the reporting of acute stroke clinical trials. We identified controlled acute ischemic stroke clinical trials reported in English over a 45-year period from 1955 to 1999 through systematic search of MEDLINE, the Cochrane Controlled Stroke Trials Register, and additional databases. We analyzed trial methodology, quality, outcome, study sponsorship, and timing of publication to identify various forms of publication bias, including nonpublication bias, abbreviated publication bias, and time-lag bias. One hundred seventy-eight acute ischemic stroke trials, enrolling 73,949 subjects, evaluated 75 agents or nonpharmacologic interventions. A greater proportion of harmful outcomes in unpublished studies (n = 4) compared with published trials (0.75 vs 0.06, p < 0.0001) and underreporting of smaller, nonbeneficial studies in acute stroke suggest nonpublication bias. Although a definite time-lag bias was not evident, nonbeneficial studies were slower to proceed from enrollment completion to publication (2.3 vs 2.0 years, p = 0.207), with an even longer delay for nonbeneficial corporate pharmaceutical sponsored trials (2.8 vs 2.1 years, p = 0.086), despite superior trial report quality scores for corporate-sponsored studies when compared with nonprofit/governmental studies (mean 69.2 +/- 95% CI 3.9 vs 53.4 +/- 95% CI 9.2, p < 0.005). Publication bias is evident in the acute stroke research literature, supporting the need for prospective trial registration.

Randomised controlled trials in Africa of HIV and AIDS: descriptive study and spatial distribution

Objectives To identify and describe randomised controlled trials on HIV and AIDS conducted in Africa and to map their spatial distribution using exact geographic coordinates.Design Construction and analysis of a...

Prospective Clinical Trial Registration

The International Committee of Medical Journal Editors (ICMJE) is a group of the world's leading medical journals whose participants meet annually to improve standards in manuscripts submitted to biomedical journals. In September 2004, the ICMJE announced a tough new stance on registering clinical trials. All trials that start enrolling participants after July 1, 2005 must register their trial in a suitable publicly accessible register before that date in order to be considered for subsequent publication in those journals.

Prospective Meta-Analysis in Dentistry

In practice, in performing systematic reviews of medical literature, the trials included are usually identified after the results have been reported. Knowledge of results may influence the definition of the review question, the criteria for study selection, the experimental and comparator treatments evaluated, and patient groups evaluated, and the outcomes examined. This raises concerns that systematic reviews may be biased in favor of results supporting the author's preconceived beliefs. This article addresses potential strategies for avoiding publication bias and related biases through the prospective identification of studies. Prospective trial registration is simply the identification of trials registered at their inception via a database accessible to concerned parties and can be used to identify trials for potential inclusion in a systematic review. A prospective meta-analysis (PMA) is a meta-analysis of studies identified, evaluated, and determined to be eligible for the meta-analysis before the results of any of those trials become known. PMA can help to overcome some of the recognized problems of retrospective meta-analyses by enabling hypotheses to be specified a priori; prospective application of selection criteria for trials; and prospectively defined analysis plans, all ignorant of the results of the trials. The prospective approach can be taken one step further through the design of the trials to be included as part of a meta-analysis at their inception. In this article we discuss practical aspects of PMA, focusing on several examples including studies of therapy for periodontal disease. We use the example of topical and systemic antimicrobial therapy for periodontal disease in diabetics to illustrate potential considerations relevant to a hypothetical fully prospective designed meta-experiment.