Building the Evidence Base: Overview of ClinicalTrials.gov
Outreach Partnership Program 2005 Annual Meeting
Saturday April 2, 2005
Marty Magee, M.A.L.S., M.S.A., Nebraska/Education Liaison
National Network Libraries of Medicine
Ms. Magee’s presentation covered the background, system design, implementation and usage of ClinicalTrials.gov, and included a demonstration. She also discussed continuing challenges and future directions.
Clinical trials are the basis for evidence-based medicine. All of the trials listed on ClinicalTrials.gov are regulated by the U.S. Food and Drug Administration (FDA), thus assuring their safety and efficacy. The model for ClinicalTrials.gov was the very successful AIDS Clinical Trials Information Service. Another impetus for its establishment was lobbying by breast cancer consumer groups, which brought further attention to dissemination of information on life-threatening diseases and conditions. The 1997 FDA Modernization Act required FDA to set up and maintain a databank of information on clinical trials of medications for serious or life-threatening diseases or conditions, to include eligibility criteria, study site locations, and a point of contact for each study, in a form readily understood by members of the public.
Responsibility for development of the database was given to the National Institutes of Health (NIH), because of expertise at the National Library of Medicine (NLM) and at the Lister Hill Center, which exist side-by-side on the NIH campus. It was determined that the database would include both federally and privately funded trials. The audience, or users, would be patients, clinicians, researchers, sponsors and public policymakers.
The goals and challenges were to meet all the needs of these stakeholders — providing accurate and timely information, providing search support for non-professionals, and presenting the information in an educational context.
During the design and testing period, the developers solicited input from many groups, including 19 different voluntary health organizations, and conducted focused testing on the data content and structure. The system first became available in February 2000. As of January 2005, Clinicaltrials.gov lists over 12,000 trials in more than 70,000 locations. Study sites are located in all 50 states and 97 different countries. The site has about 7 million page views per month. People access it directly and from other health-related sites.
Ms. Magee conducted a demonstration of ClinicalTrials.gov, showing its ease of access. In conducting a search, the user has three choices: typing words into a query box similar to that on Google.com, doing a “focused” search, or browsing by condition, sponsor, or recruitment status. The system is very flexible, listing information on the specific topics and also on closely related terms. It recognizes spelling mistakes. It also allows searching within results, so that the user has the option of refining the search.
Users can find trial locations that specify particular cities, age groups in the study, and the phase (I, II or III). Phase I studies involve a few people and focus on safety; Phase II studies, which involve more people, test efficacy as well as safety, and Phase III studies look at those factors and gain information about side effects. In the fourth or post-marketing phase, testing on side effects associated with long-term use are conducted.
Users can find out whether a study is being funded by the NIH or the pharmaceutical industry, whether the study is still recruiting participants, and who is eligible for the study. The Resources section offers general information on understanding clinical trials and their risks and benefits, and links users to the various Institutes at NIH. “What’s New…” shows studies that have been recently started, and “Clinical Trials in the News” links to journal publications and press releases that announce clinical trial results.
From ClinicalTrials.com, users can also link to consumer information available from the NLM’s MedlinePlus® and to scientific citations in PubMed. As with anything that comes from the National Library of Medicine, there is no requirement for a user name or password, and there is no risk of spam! Outreach Partners should especially make their target audiences aware of MedlinePlus®, which contains free information on thousands of health topics. Everyone knows that a huge amount of great, and also bad, information is on the Internet. To help people evaluate the quality of a website, anyone can go to MedlinePlus®, search for “evaluate,” and see a list of 10 questions to ask. Everything on MedlinePlus® has been reviewed by NLM, so users can be confident that it is credible and reliable. “Go Local,” a new initiative on MedlinePlus®, lists health services related to a particular topic in a chosen geographical location; so far, this is only available for Missouri and North Carolina, but other states will be added. Drug information, a topic on the front page of MedlinePlus®, comes from MedMaster, which is the source used by many pharmacies in dispensing medicine. You can also find interactive, self-paced health tutorials on many topics; they are like slideshows with audio, and are especially effective for low-literacy users or those for whom English is a second language. In addition, by clicking on “Español,” the web site converts from English to Spanish.
PubMed is a database that has an index of 4,500 biomedical journals published all over the world, going back to the 1950s. It provides citations of articles and abstracts, if available, but in only a small percentage of cases will you gain access to the full article. Free articles can be accessed by adding a “string” to the search criterion: e.g., “schizophrenia AND shock treatment AND free full-text [sb].” Clicking on the green space next to the citation will take you to the publisher’s site and a PDF file of the article. You may also search for full-text articles on PubMed Central, the NIH’s free digital archive of biomedical and life sciences journal literature. Generally, however, you will need to go to a library to read recently-published articles. NLM recently made available a Genetics Home Reference page that may be of particular interest to Outreach Partners.
Ensuring high quality of the data, currency and access to “just-in-time” resources (hyperlinks to other resources), on ClinicalTrials.gov or on other NLM web sites, requires working closely with all of the institutes at NIH and other agencies. Some of the continuing challenges include providing additional views regarding treatments, assuring data quality and readability, and providing Spanish language information retrieval.
During the past year or so, there has been considerable attention paid to incidents in which positive results of industry-sponsored clinical trials were publicized, but negative results were not announced. A number of organizations, including the Society for Clinical Trials, the American Medical Association, and the International Committee of Medical Journal Editors have called for public registration of clinical trials. PhRMA, the organization of pharmaceutical researchers and manufacturers, the World Health Organization and Consumer Union have also weighed in. There have been Congressional hearings, and the Fair Access to Clinical Trials (FACT) Act was introduced in Congress in February of 2005. Up until now, industry submissions to ClinicalTrials.gov have been optional; if passed, FACT will set out a number of requirements for comprehensive inclusion of information about privately-funded as well as publicly-funded trials. No further action has taken place on this legislation since June of 2005.
Ms. Magee ended by reminding everyone to utilize the resources available through the National Network Libraries of Medicine (http://www.nnlm.gov/) and to call the toll-free number (1-800-338-7657).
Questions and Answers
In response to a plea for more resources for Outreach Partners, Ms. Magee said that NLM offers grants to groups interested in partnering to share evidence-based information.
Disclaimers
* This document is intended to summarize a speaker presentation at the NIMH Outreach Partnership Program’s Annual Meeting and is not an official statement or opinion of the NIMH. This information is in the public domain and may be used or reproduced for educational purposes without additional permission from the NIMH.
