Hello Tom,
Whew. I feel like I can write (or *am* writing!) a book. I’ll take
your questions one at a time, below. But if you post additional
questions in the future, there’s one I’d like you to answer as well:
–what’s more important to you – to be the very first one on your block
to know about an adverse reaction, or to be the one who knows the
most?
I’m sure your answer is going to be “both”, but give the question some
thought. It would be a help (to me, at least!) to know where you’re
coming from on this.
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1) General recommendations
[please forgive me if I’m stating the obvious here]
–use drug names *and* their synonyms for searching
Many search systems allow “OR” searching so that you can combine
several synonyms into a single search. For example, a search could be
for (tylenol OR acetaminophen), and the results would include
studies/articles that contain either term. The ChemIDplus system that
Tehuti-ga identified for you in an earlier question would be helpful
here:
http://answers.google.com/answers/main?cmd=threadview&id=172157
Be aware that drugs may be marketed overseas under different names
than the popular name used in the U.S.
–search first for the drug name (and synonyms) alone.
For many drugs, there simply may not be an extensive body of
literature – the number of published studies may be in the dozens.
For these drugs, it is feasible to simply amass every publication
available and scan them for relevant information.
–in other cases, a search on the drug name alone will reveal hundreds
or thousands of reports – too many to manually review. In this event,
search results can be narrowed down by:
1. Time – search only for articles in the past X weeks/months/years –
whatever time frame meets your research needs. Most search systems
provide some sort of date selection function.
2. Adverse effect – search for articles that include the drug’s name
as well as other key phrases of a general nature (“adverse effects”,
“side effects”, “case report” etc.) as well as more specific phrases
(such as “carcinogenicity”, “liver damage”, “reproductive toxin”,
etc.). The actual terms chosen depend, in large measure, on what you
are looking for, and what the thesaurus of the database looks like –
I’m sure Tehuti-ga can offer some more detailed advice on this.
3. Field searches – again, many search systems offer an option to
focus a search on particular fields – the title of an article,
keywords, journal source, etc. These can be useful in taking a list
of thousands of preliminary results, and paring it down to a
manageable number.
4. Proximity searches – this is less universal than other search
tools, but when it’s available, it can be awfully handy.
If X and Y are your two terms of interests, the proximity search
usually takes the form of [X NEAR Y] or [X w/# Y] or [X and Y in the
same line/sentence/paragraph/page]. The first will look for the terms
close together in a text (each search system has its own particular
protocol for interpreting “NEAR” – some searches also include ADJ for
“adjacent to”). The second will search for terms that are within a
specified number of words of one another: you get to select the value
of #. The third will look for the terms together in the same unit of
text, according to your selection. If you’re not familiar with these
types of searches, some good examples can be found at the search help
page at a Dept. of Energy site:
http://search.dis.anl.gov/plweb-cgi/iopcode_mhrex.pl
towards the bottom of the page is: Table 5 - Summary of Query
Operators.
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Of course, none of these suggestions help with the question of *where*
to search. As you are finding out (or perhaps, already knew) there
are many different sources of information regarding adverse effects of
medicines. The “where” question depends in very large measure on
what, particularly, you are trying to find out. Perhaps in a future
question you can provide some additional specifics, and ask a
researcher to craft a specific search strategy for you.
One major source that I want to mention here, though, is the Adverse
Events Reporting System – AERS – at FDA, which has already been
mentioned several times in other answers. I spoke to a staffer at FDA
who told me they handle about 270,000 reports in a typical year. The
entire AERS data set is available for purchase, if you’re interested
in managing a fairly sizable database. Information regarding
purchase, on either a one-time or ongoing subscription basis, can be
found at FDA’s site:
http://www.ntis.gov/search/product.asp?ABBR=SUB5460&starDB=GRAHIST
“The Adverse Event Reporting System (AERS) of the Center for Drug
Evaluation and Research is a computerized data base of drug adverse
reactions reported by health professionals and others. The system
contains only adverse reactions detected and reported after marketing
of the drug during the quarter. The information is not cumulative. The
primary purpose for the AERS data base is to serve as an early warning
or signaling system for adverse drug reactions not detected during
premarket testing. The files included on the CD-ROM are: (1)
Information on demographic and administrative information and the
initial report image ID number (if the image is available); (2) Drug
information on the case reports; (3) Reaction information on the
reports; (4) Patient outcome information on the reports; (5)
Information on the source of the reports. Historical Data may be
ordered through our Sales Desk at 1-800-553-6847. January-December
1999, Order Number PB2000-500054, price $360; January-December 2000,
Order Number PB2001-500048, price $360; January-December 2001, Order
Number PB2002-500060, price $360.”
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2) I know that some medical works published in medical articles can be
mainly designed for other reason than for detecting adverse events,
but looking carefully to the results, you may be able to find adverse
events. How do suggest to overcome this issue?
Again, there’s a matter of numbers here. If you’ve conducted a search
and have uncovered three studies on a particular drug, then it’s
feasible to read each of the studies word for word and look for
evidence of adverse reactions that may not have been highlighted by
the authors.
But what to do if you have hundreds of potential studies to go
through? One answer is that the tools that I mentioned above under
“General recommendations” are the very same ones that could help you
here. An author may have dismissed a case of cancer, as a
happenstance, rather than an outcome related to drug exposure – in
other words, the study may treat the cancer as statistically not
significant, rather than as an “adverse reaction”. But nevertheless,
the presence of cancer in a test person or animal would not go
unmentioned, so that a search on the terms: [“drug name” and cancer]
should flag this report as one that is worthy of more detailed
attention.
I also want to mention – though I suspect you are already aware of
this – the field of meta-analysis. Meta-analysis combines information
from several related studies (in your case, studies of the same drug)
with the aim of increasing the overall statistical power of the
analysis. In theory, as well as in practice, a meta-analysis of
combined studies can reveal a statistically significant adverse effect
of a drug, that was not revealed by any of the individual studies.
An example of a drug-related meta-analysis can be found at the
Schaffer Library of Drug Policy site at:
http://www.druglibrary.org/schaffer/Misc/driving/s13p1.htm
“Medicines and Driver Fitness - Findings from a Metaanalysis of
Experimental Studies as Basic Information to Patients, Physicians and
Experts”.
I’m not aware of any means of automating meta-analysis – it is a form
of professional research by trained humans, rather than an outcome of
a clever machine. However, there is certainly the potential here to
clarify adverse effects that may otherwise have been missed, and for
this reason, may be of importance to your work.
3) In one of the reference links you gave me in a previous answer,
FDA recommends to take account of the pharmacology of the product or
drug under surveillance, in order to predict the adverse event that
may arise. How do you relate this with potential search strategies in
databases?
Once again, I want to emphasize that if you are researching a
relatively obscure drug that does not have a great many recent studies
in the literature, there may be no need for the pharmacological
approach you are describing, as it may be possible to review all
available information. Hence, there would be no need to narrow your
search by trying to predict relevant adverse effects.
I cannot go into a full discourse here on applying the tools of
pharmacology – pharmacokinetics, pharmacodynamics, and so on – to
predicting likely adverse effects. The basic approach here is to
combine an understanding of a drug’s chemistry, means of action,
metabolism in the body, and chemical energetics, to make reasonable
guesses about biologically-important drug properties, such as: how
does the drug partition in the body (proportion that goes to blood,
kidney, bones, etc); how long is the half-life of the drug in
different body compartments (is it water-soluble and quickly excreted,
or fat-soluble resided in the body for a long time); what are the
likely metabolic products of the drug (and what is the toxicity of
each of these chemicals).
The literature of a particular drug may well contain much of this type
of information, and could be isolated by using appropriate search
terms. But again, the actual search that you would want to conduct
depends very much on what drug you are researching, what search system
you are using, and what question(s) you want answered.
You can get a feel for what the pharmacological approach looks like by
reviewing the notes of a college-level course on pharmacokinetics:
http://www.boomer.org/c/p1/
“A First Course in Pharmacokinetics and Biopharmaceutics”.
I’m not sure what else to add on this topic – it is simply too broad
in scope to be able to readily narrow down to particular search
strategies for an unspecified chemical.
For this topic, as for all the information I’ve provided here, just
post a Request for Clarification if you want any additional
information.
And one last thing: somehow, in my earlier work, I overlooked an
important resource on adverse events reporting – the World Health
Organization. Information about their reporting system can be found
here:
http://www.who-umc.org/aboutumc.html
WHO adverse events database
It's worth a look.
So long...for now. |
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