Study Finds Outcome Data in Clinical Trials Reported Inadequately, Inconsistently

Philadelphia, May 15, 2014 /3BL Media/ – There is increasing public pressure to report the results of all clinical trials to eliminate publication bias and improve public access. However, investigators using the World Health Organization’s International Clinical Trials Registry Platform (ICTRP) to build a database of clinical trials involving chronic pain have encountered several challenges. They describe the perils and pitfalls of using the ICTRP and propose alternative strategies to improve clinical trials reporting. This important and insightful study is published in the August issue of the journal PAIN^®.

U.S. law already requires posting summarized results on ClinicalTrials.gov, a service of the National Institutes of Health, within one year of study completion for certain categories of industry-sponsored trials. Legislation mandating data publication within one year of study completion, irrespective of outcome, is under consideration in the European Union. Yet compliance with the U.S. law is poor.

“Although clinical trial registries facilitate public access to basic trial information, we found that access to unbiased trial results is still inadequate. A distressingly large number of trials have no published results at all or are mentioned only in sponsor press releases. Recent analyses have found that only 25-35% of clinical trials required to post study results on ClinicalTrials.gov actually do so,” comments senior investigator Michael C. Rowbotham, MD, scientific director of the California Pacific Medical Center Research Institute in San Francisco.

The investigators drew on their experience with the Repository of Registered Analgesic Clinical Trials (RReACT) database, a scorecard for analgesic clinical trials for chronic pain (sponsored by an FDA grant to the University of Rochester), to describe the challenge of constructing a global open-access database of clinical trials and trial results. They focused on three frequently studied chronic pain disorders: post-herpetic neuralgia, fibromyalgia, and painful diabetic peripheral neuropathy. The initial build of RReACT was limited to randomized trials registered on ClinicalTrials.gov with a primary (or key secondary) outcome measure assessing analgesic drug efficacy. The database was then expanded to report on all of the primary registries in the ICTRP, and investigators analyzed trial registration, registry functionality, and cross-registry harmonization, using a comprehensive search algorithm to find trial results in the peer-reviewed literature and grey literature. A total of 447 unique trials were identified, with 86 trials listed on more than one registry.

The ICTRP provides a single search portal to 15 primary registries, including ClinicalTrials.gov. ICTRP primary registries follow International Committee of Medical Journal Editors (ICMJE) guidelines and must have a national or regional focus, government support, nonprofit management, free public access, and an unambiguous trial identification method.

ClinicalTrials.gov is the largest ICTRP database, with more than 152,000 trials globally. The EU Clinical Trials Register (EU-CTR) is the second largest, with more than 21,000 trials. Current Controlled Trials (more than 11,000 trials), the oldest global registry, is hosted by BioMed Central (part of Springer Science + Business Media, a for-profit scientific publisher specializing in open-access journals). Five national registries each contain fewer than 1,000 trials. All ICTRP registries provide information about study design (i.e., randomization, blinding, control groups, inclusion/exclusion criteria, and outcome measures) and current study status. Not all ICTRP registries track study changes, list additional study identifiers, or provide links to publications.

“We identified several perils and pitfalls of using the ICTRP,” says Dr. Rowbotham. “Manual searches are necessary, as ICTRP does not reliably identify trials listed on multiple registries. Searching ICTRP as a whole yields different results from searching registries individually. Outcome measure descriptions for multiply-registered trials vary between registries. Registry-publication pairings are often inaccurate or incomplete. Ideally, a PubMed search on the trial registration number would reveal all study-related articles, but a recent analysis showed that about 40% of journal publications failed to include registration numbers. And grey literature results--such as trial-specific press releases or company statements, information found on the websites of pharmaceutical companies, and abstracts of poster/platform presentations at scientific meetings--are not permanent.

“Creating a single global registry would solve many of the problems we describe here,” he continues. “However, international politics and funding limitations suggest this is a challenging goal. Despite its flaws, ICTRP does at least offer a single search portal.”

The investigators offer several suggestions for improving the current situation. In addition to the simple remedy of including trial registration numbers on all meeting abstracts and peer-reviewed papers, they propose specific strategies to identify multiply-registered studies and ensuring accurate pairing of results and publications.

“Compliance might improve, especially for difficult-to-publish ‘negative’ studies, if posting results on trial registries could be made simpler and uniform. Alternative solutions to the problems of publication bias and selective reporting should also be explored. These might involve including journals specializing in publishing ‘negative’ results, creating user-friendly and publicly available databases to publish results, and raising the awareness of authors, reviewers, and editors about these issues,” concludes Dr. Rowbotham.

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Notes for editors
“RReACT Goes Global: Perils and Pitfalls of Constructing a Global Open-Access Database of Registered Analgesic Clinical Trials and Trial Results,” by Troels Munch; Faustine L. Dufka; Kaitlin Greene; Shannon M. Smith; Robert H. Dworkin; Michael C. Rowbotham (DOI: http://dx.doi.org/10.1016/j.pain.2014.04.007). It appears online ahead of PAIN^®, Volume 155, Issue 8 (August 2014) published by Elsevier.

Full text of the article is available to credentialed journalists upon request. Contact Terry Materese at +1 215 239 3196 or painmedia@elsevier.com for copies. Journalists wishing to interview the authors should contact Dean Fryer, Media Relations Manager, California Pacific Medical Center, at +1 415 600 7484, +1 415 232 6463 (pager), or FryerD@sutterhealth.org.

About PAIN®
PAIN^®, the official journal of the International Association for the Study of Pain^® (IASP^®), publishes 12 issues per year of original research on the nature, mechanisms, and treatment of pain. This peer-reviewed journal provides a forum for the dissemination of research in the basic and clinical sciences of multidisciplinary interest and is cited in Current Contents and MEDLINE. It continues to be ranked No.1 out of the 29 journals in the Anesthesiology category, according to the 2012 Journal Citation Reports, published by Thomson Reuters.

About the International Association for the Study of Pain^® (IASP^®)
IASP^® is the world's largest multidisciplinary organization focused specifically on pain research and treatment. It is the leading professional forum for science, practice, and education in the field of pain, bringing together scientists, clinicians, health-care providers, and policymakers to stimulate and support the study of pain and to translate that knowledge into improved pain relief worldwide. Founded in 1973, IASP has nearly 8,000 members from 133 countries and in 90 chapters.

About Elsevier
Elsevier is a world-leading provider of information solutions that enhance the performance of science, health, and technology professionals, empowering them to make better decisions, deliver better care, and sometimes make groundbreaking discoveries that advance the boundaries of knowledge and human progress. Elsevier provides web-based, digital solutions — among them ScienceDirect, Scopus, Elsevier Research Intelligence and ClinicalKey — and publishes nearly 2,200 journals, including The Lancet and Cell, and over 25,000 book titles, including a number of iconic reference works.

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Media contact
Terry Materese
Tel: +1 215 239 3196
Cell: +1 215 327 9934
painmedia@elsevier.com