Definitions:
Clinical Trial Registry: A database containing entries with basic information about a clinical trial. Follow this link to the CIRCARE web page on Clinical Trial Registries
Study Results Database: A database with summaries of (mostly) unpublished clinical trials.
PhRMA's Clinical Study Results Database: http://www.clinicalstudyresults.org/
Comments: Commercial study results database with summary results of clinical trials sponsored by drug manufacturers. Pro: most extensive holding; allows search by generic or trade name of drug, disease, or sponsor-manufacturer. Con: no summaries of studies submitted for publication; no (or few) phase I studies; phase II study reports limited to studies supporting labeled indications; few entries identify investigators or study sites; participation is voluntary; some drugs not included.
American Society of Clinical Oncology (ASCO) Annual Meeting Abstracts: http://www.asco.org/ac/1,1003,_12-002629,00.asp
Comments: Effectively a study results database where you can search for cancer research abstracts presented at meetings between 1995-2004; phase I studies tend to be over-represented because they may be described in abstracts rather than published articles; ASCO is the professional organization of clinical oncologists.
Another way to locate information about unpublished studies is to trudge through the FDA Drug Approval Package for the drug of interest. The Medical Review section(s) lists and evaluates studies conducted under the IND associated with the New Drug Application. While this sounds ideal, coverage varies; some Medical Reviews have exhaustive descriptions of each and every trial from phase I to phase III, while others have brief entries, lists only, or nothing but phase III trials. Once in a while information about studies is in the Administrative Documents section(s). Drug Approval Packages can be enormous with 36-part Medical Reviews, and not every Medical Review has a table of contents. If there is a table of contents, it's usually somewhere in the first 10 pages of part 1 of a multi-part Medical Review. The information may be difficult to understand because it's written for by FDA drug reviewers for FDA drug reviewers.
To find the FDA Drug Approval Package, enter the name of the drug in FDA drug database at http://www.accessdata.fda.gov/scripts/cder/drugsatfda/. If there are generics or different strengths the search may provide several different links; select the link to the drug name followed by the lowest
NDAnumber (you may have to try each link; don't give up). If you've selected the correct link, it will take you to theDrug Detailswhere you should see a link at the top titledApproval History and Related Documents.This link will take you to the drug'sApproval History.Go to the earliest entry and look for the link titledReview.To get an idea of what sort of information you can find, here are two examples of FDA Drug Approval Packages:
Ketek (Telithromycin) Tablets. Company: Aventis Pharmaceuticals, Inc. Application No.: 021144. Approval Date: 4/01/2004. Accessed on 2006-05-23 at: http://www.fda.gov/cder/foi/nda/2004/21-144_Ketek.htm
Trovan Tablets & Trovan I.V. (Trovafloxacin Mesylate & Alatrofloxacin Mesylate). Company: Pfizer. Application No.: 20-759 & 20-760. Approval Date: 12/18/1997. Accessed on 2006-05-23 at: http://www.fda.gov/cder/foi/nda/97/020760a.htm
GlaxoSmithKline Clinical Trials Registry: http://ctr.gsk.co.uk/welcome.asp
Comments: Commercial study results database and clinical trial registry with expanded description of trial design. Information provided by GSK Inc., sponsor of the trials; see comments (above) on PhRMA's Clinical Study Results Database.
Forest Laboratories Clinical Trials Registry: http://www.forestclinicaltrials.com/CTR/CTRController/CTRWelcome
Comments: Commercial study results database and clinical trial registry. Information provided by Forest Laboratories, Inc., sponsor of the trials; standard industry summaries organized by drug and condition are posted at the
Completed Studieslink; see comments (above) on PhRMA's Clinical Study Results Database.
LillyTrials Eli Lilly and Company Clinical Trials Registry: http://www.lillytrials.com/
Comments: Commercial study results database and clinical trial registry. Information provided by Eli Lilly and Company, sponsor of the trials; useful link to
Initiated Trialswith links to trial summaries; see comments (above) on PhRMA's Clinical Study Results Database.
International Federation of Pharmaceutical Manufacturers & Associations: http://www.ifpma.org/clinicaltrials.html
Comments: Commercial clinical trial registry and study results database. Pros: outstanding comprehensive search with option to search multiple databases from the IFPMA search portal. Cons: search results are awkwardly formatted and difficult to read; see comments (above) on PhRMA's Clinical Study Results Database.
A (very) few sponsors have begun to post links to published study results on Clinicaltrials.gov: http://www.clinicaltrials.gov/
Autism Tissue Project:
Approved Projects. Accessed on 2007-02-09 at: https://atpportal.org/pls/htmldb/f?p=108:400:8088999459172318::NO:::
Research Project Results. Accessed on 2007-02-09 at: https://atpportal.org/pls/htmldb/f?p=108:96:8088999459172318::NO (NB: full text articles provided)
If you're just beginning to gather information about a drug, study results databases should be the last step, not the first. Use the FDA Drug Information database at Drugs@FDA to locate Patient Information Sheets, Professional Prescribing Information (e.g., the drug labeling information), and Drug Approval Packages. Drug Approval Packages contain FDA evaluations of all trials conducted under an IND that becomes part of the application for marketing approval, whether or not the trial demonstrated efficacy for the proposed indication for use. In theory, this should be comprehensive because without an IND, in the case of a new drug, the sponsor cannot conduct studies. The catch though, is that you won't find information about studies testing the drug for indications other than the indication for use for which marketing approval was granted, or previously approved indications for use. The reason for this is that INDs are relatively narrow, and separate INDs are required for testing in different diseases or disorders. Federal law and regulations also limit what FDA can request from drug marketing approval applicants.
You can search PubMed at the National Library of Medicine to find published studies. You can find reliable sources of information about medical treatment on our Medicine and Medical Treatment page. Although some study results databases also provide information about published studies, they're primarily useful for locating unpublished studies.
Use these resources wisely. The best source of information about your health and any medicines prescribed for you is your licensed primary care physician or medical specialist. Always consult with your physician when you have questions about your health. Aside from this obvious caveat, it's difficult to offer many suggestions about these resources. While using clinical trial registries is relatively straightforward, study results databases present some problems. If you're accustomed to reading clinical trial protocols, NDAs, or FDA Drug Approval Packages, the information contained in most study results databases entries is likely to seem woefully inadequate. It's much more likely, however, that many consumers will find the information overwhelming or otherwise confusing because the summaries are written for physicians.
Perhaps the best strategy might be to figure out what your questions are before you start your search. If you want to know why your physician prescribed a drug, these resources won't answer your question. Only your physician can do that.
The question will this drug work for me
is best answered by your physician.
And remember: no study can demonstrate something doesn't work. Huh? It's useful to understand what a study can and cannot demonstrate. A controlled clinical trial (a fancier phrase for many drug and device studies) is designed to demonstrate cause and effect, e.g., that Drug A cures Group B Step infection in newborns. Such a study is controlled
to limit or (preferably) exclude extraneous variables and chance, and so permit investigators to evaluate the efficacy of Drug A on Group B step infection in newborns. Even the best designed controlled clinical trial can only confirm or fail to confirm that A (a drug or other treatment) caused B (the observed effect). A controlled clinical trial in which investigators don't observe the proposed treatment effect is a study that failed to confirm A caused B. This is not the same thing as saying A does not cause B – this may seem obvious or trite, but it's an important point that often gets overlooked. Put differently, a controlled trial cannot demonstrate a negative, e.g., that A isn't an effective treatment for B.
If you want to know whether clinical trials have been conducted with a drug, and for what indication, you may or may not be to able to find this information. All commercial, nonprofit, and university-sponsored clinical trial and study results databases are voluntary.
When searching in study results registries, consider some or all of the following:
severe,
mild,or otherwise qualified. The results are more likely to be applicable to you if your condition is the same as the test subjects.
N,e.g.,
N=279.In general, but not always, larger numbers permit more definitive conclusions.
Understand the limitations of the study results registry. Read the fine print and any information on linked pages titled About
. Not all registries contain the same information. For example, the Clinical Study Results Database Frequently Asked Questions at the PhRMA-sponsored study results registry explains that the database provides summarized results of hypothesis testing
studies and well controlled clinical trials
of marketed drugs. Phase I and many or most phase II studies are not included because they are labeled exploratory
studies, rather than hypothesis testing
studies. Although this distinction is rather thin (by definition the purpose of research is to answer a question; all studies are hypothesis testing
studies), it's PhRMA's prerogative to make. It's up to the user of the database to be aware of what's included and what's not.
The other serious limitation of any study results registry is lack of peer review. Since nobody is making treatment or policy decisions based on studies with equivocal or disconfirming results (hopefully), this is less problematic.
Understand the meaning of the terms used.
An
adverse eventis:
Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.An
adverse drug reactionis:
A response to a drug which is noxious and unintended and which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of disease or for modification of physiological function.Source: FDA Guidelines for Industry, Clinical Safety Data Management: Definitions and Standards for Expedited Reporting. March, 1995. Pp. 2-3. Accessed on 2004-12-29 at: http://www.fda.gov/cder/guidance/iche2a.pdf
An excellent straightforward article about the differences between a side effect, an adverse event (or effect), and an adverse drug reaction is:
Nebeker JR, Barach P, Samore MH. Clarifying Adverse Drug Events: A Clinician's Guide to Terminology, Documentation, and Reporting. Ann Intern Med. 2004;140:795-801. Accessed on 2006-03-02 at: http://www.annals.org/cgi/reprint/140/10/795.pdf
Drug manufacturers created these databases in response to concerns that equivocal or disconfirming studies were not published, or that adverse event reporting and disclosure was less than ideal. Dozens of news stories quoted anxious patients demanding to know what the real risk
of taking Wonder Drug A was. It's fairly clear that what these (justifiably) concerned people meant was not in fact risk,
but rather the likelihood of serious harm.
The question is more complicated than it might appear. Risk has two elements: magnitude, e.g., is it severe, (or lethal), or permanent, and likelihood of occurrence, e.g., how often does it happen, and to whom. Risk needs to be evaluated against the prospect of benefit (or the risk of doing nothing) and against available alternatives, and this is a task for you and your primary care physician.
Most, if not all, summaries of study results have tabular presentations of adverse events and adverse drug reactions. The AEs and ADRs (usually) are listed in alphabetical order next to the percentage of study subjects who experienced them. AEs and ADRs are most often (and should be always) listed by their proper medical names, so plan to use a medical dictionary.
If some subjects received a placebo, percentages of those reporting adverse events will also be included in the tables. In some cases, if the same number of subjects receiving the drug and receiving placebo experience similar events with approximately the same frequency, this may help investigators determine if the event is more likely to be caused by chance than by the test drug.
If the number of adverse events or their severity concern you, check to see how often it was reported among subjects receiving placebo. The greater the difference between the two, the more it suggests the effect might be caused by the drug, but keep in mind the distinction between association (adverse events) and causation (adverse drug reaction).
Is it a Phase I study? If so all AEs are recorded as ADRs by convention.
Skim through the summary and try to find out how many subjects finished the study. While a high number of dropouts doesn't prove anything, dropout rates in excess of 50% in an outpatient study with high rates of serious adverse drug reactions might suggest subjects had difficulty tolerating the drug. Don't be too concerned with dropout rates because subjects drop out of clinical trials for a variety of reasons and do so regularly. The dropout rate, however, is important for analysis and interpretation (obviously), and it's important to know the extent to which it is or is not related to adverse drug reactions.
Keep in mind that all drugs, devices, etc. have adverse events associated with their use; some cause adverse drug or device reactions, and one of the purposes of clinical trials is to detect and record them.
You can find links to FDA drug information, university-sponsored information, specialized information, resources for locating the professional prescribing insert for drugs, adverse event information, and much more on the following pages on our web site:
Last Updated: 2007-09-05
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