July/August 2012 CyberSelection: ClinicalTrials.gov

ClinicalTrials.gov is a registry and results database of clinical trials supported by federal and private healthcare research facilities and conducted in the United States and around the world. Authorized by federal mandate in 1997 and managed by the National Institutes of Health, the database went live in February 2000 and currently gives information about the purpose, location, and participant requirements of more than 125,000 clinical trials in all 50 US states and nearly 180 countries.

A primary purpose of the FDA Modernization Act that enabled ClinicalTrials.gov is to recruit human volunteers for the study of new drugs, diagnostic procedures, vaccines, and experimental therapies. The site makes it easy for patients, their care providers, and  healthcare professionals to find out about specific trials that are planned, taking place, or completed.

Searching for Trials

A Basic Search page (http://clinicaltrials.gov/ct2/search) offers a single search box, where you can enter a word or a phrase to describe a medical condition or intervention. A search on the disease polymyositis, for example, brought 43 results: interstitial lung disease brought 319. Example searches indicate that you can add a location or combine  words with AND (capital letters). I found 43 study results for interstitial lung disease AND Ohio. The results page ranks studies in relevance order and displays the study name and status, condition, and intervention. Study status may indicate Recruiting; Not yet Recruiting; Active, Not recruiting; Completed; Terminated; Completed, Results; or Unknown, in which case the status has not been confirmed in two years.

Regardless of a study's status, much more information, including eligibility, sponsors, phase, contacts, and an informative description, is available on a detailed record page by clicking the study name link.  Once you have viewed detailed records and seen the record structure, you may be inclined to use the Advanced Search page (http://clinicaltrials.gov/ct2/search/advanced), which is also the screen that appears if you select Refine Search after viewing results of a Basic Search. Here there are numerous field options, some with drop-down or checkbox options, that help you refine criteria by geographic location, trial phase, age group, funding,  sponsors, and more. A nice feature of the ClinicalTrials.gov search form is that each field label is hyperlinked; when you click the label a pop-up window appears with relevant information for that field. You can even move the pop-up around on your screen so you can see it and the search form at the same time.

More Search Options and Help

You can bypass both the Basic and Advanced Search functions, however, and click on the Studies by Topic tab to browse all records by Condition, Drug Interventions, Sponsor/Collaborators, Locations, Rare Diseases, and Dietary Supplements. Each of these major topics can be approached by an A-Z list of subtopics or by a series of categories and subcategories. For example, I found 24 studies on calcium supplements in the Dietary Supplements category listing by clicking first on  Mineral and then on Calcium Supplements. There are 39 studies on Beta Carotene, which is under the Vitamins listing in the Dietary supplement topic. You may be surprised at some of the topics that receive study funding and are listed under the Herbal and Botanical topic or Other Dietary Supplements: Black Cohosh, Cayenne, Lutein, Citrate, and Omega 3 Fatty Acid, which itself has a whopping 507 studies.

For extensive or detailed research, you can make use of the MeSH descriptors that accompany any detailed record. Although they are not linked, you can use a MeSH term to refine a search in ClinicalTrials.gov or to extend an investigation into the PubMed or MEDLINE databases. An excellent Help page (http://clinicaltrials.gov/ct2/help/help) provides assistance with Basic and Advanced searching, Refine Search, Search Expressions, and medical research terminology and process.

Another superb search aid is available through the Search Details tab that appears on the initial results page. A search on "macular degeneration" gave me 783 results; when I clicked Search Details I found a short list of Recognized Terms and Synonyms that I could use to extend the search if needed. There was also a more extensive, hyperlinked list of Related Terms. Directions said that clicking on a term would narrow the existing search by adding the new search term. If the search became too narrow, the instructions advised, return to the Refine Search page and remove terms.

A not-to-be-missed search aid is the Glossary of Clinical Trials Terms  (http://clinicaltrials.gov/ct2/info/glossary), with definitions of approximately 100 specialized terms, aimed at the consumer. Though some of the terms defined here are specific to the ClinicalTrials.gov site, most are not, and anyone researching clinical trials should study this glossary. More background information is available from  a list on another page (http://clinicaltrials.gov/ct2/info/index). Understanding Clinical Trials (http://clinicaltrials.gov/ct2/info/understand) details the entire process of trials from a health consumer point of view, through an FAQ format of 20 questions; answers also contain hyperlinks that lead back to the glossary.

Further instruction in the use of ClinicalTrials.gov is available in the form of a series of videos of 2-4 minutes each. A complete list of the Flash videos is available at http://www.nlm.nih.gov/bsd/viewlet/ct/index.html.

Trial Results

A Help page About the ClinicalTrials.gov Results Database (http://clinicaltrials.gov/ct2/info/results) describes the "results" side of this registry and results site. Results reporting to the public for registered studies was made mandatory with the Food and Drug Administration Amendments Act of 2007, which requires that a responsible party submit "basic results" information not later than one year after the "primary completion date" of a study.

Obviously not all search results will show study results, as many trials are ongoing or not even begun. Some completed trials will have results, as well as some that were terminated. If a study has results reported, a Has Results note will appear in the status column on the brief search results list. (You can also limit an Advanced Search to those with results.) Click the title of the study to go to the detailed page and then click on the Study Results tab. In my search on "macular degeneration" I found "A Study On The Efficacy Of Macugen Injections In Patients With Neovascular Age-Related Macular Degeneration In Real Life. (MACURELI)"

(http://clinicaltrials.gov/ct2/show/results/NCT00549055?term=%22macular+degeneration%22&rank=20). Study results are reported in an extensive tabular format. These results on its trial in Belgium were reported by Pfizer, the sponsor of the trial and co-developer with Eyetech Pharmaceuticals of the drug Macugen.

Who's Doing What

Because of its detailed structure, with sponsor information, ClinicalTrials.gov is an excellent site to use for tracking the pipeline of specific drug companies or determining the pharma companies interested in particular conditions or therapies. By searching Pfizer in the Sponsor field, specifying Open Studies in the Recruitment field, and checking the Phase 1 checkbox, I found 97 studies for which Pfizer is recruiting subjects or planning, but "not yet recruiting."

I searched for Lewy Bodies as Condition and found 32 results. That prompted me to click on the Display Options button and discover that I could select more fields to display in my brief results list. I checked Sponsor/Collaborator and Phase and was able to review results in two screens, discovering quickly that there are many hospitals and research centers investigating various drugs and other procedures for this type of dementia.

After discovering the power behind the Display Options button I also investigated the Download Options button at the bottom of a brief results list. I was equally impressed.  You can download complete studies or studies with results in XML. Or you can select just the fields you want and download them in plain text, tab-separated values, comma-separated values, or XML.

In summary, ClinicalTrials.gov is a superb site, one of many excellent and free sites of the National Institutes of Health/National Library of Medicine. It is certified by Health On the Net Foundation (HON; www.hon.ch/) and complies with the HONcode standard for health information. ClinicalTrials.gov does not host or receive funding from advertising and does not display commercial content. The information you receive is trustworthy and timely; the interface is clean, clear, and elegant; discoverability functionality is sophisticated but intuitive. ClinicalTrials.gov is highly recommended for medical, health, and business research, and for healthcare consumers.

Susanne Bjørner provides editorial services to publishers, librarians, authors, and researchers from a base in Spain. Contact her at bjorner@earthlink.net or www.bjorner.info.