Wednesday, September 19, 2007

The Drug Safety Blindfold

A recent study in the Archives of Internal Medicine found that serious adverse drug events reported to the FDA were up by a large margin (260%) from 1998-2005. A major problem with any such investigation, and acknowledged by the authors, is that adverse events are only rarely reported when they occur. Thus, their findings are nearly certainly an underestimate, likely by a large margin.

Why the upsurge? The authors stated:

The increase over time was largely explained by increases of just 1 type of report – expedited reports from manufacturers of new, serious events not on the product label. Of the increase of 54,876 additional events in 2005 compared with 1998, expedited reports accounted for 48,080 (87.6%) of these events.

Wait a second -- a large chunk of these reports are from the manufacturer regarding events that are not on the product label, meaning events that the manufacturer claims do not happen while taking the drug? I really hope I am missing something here. At first glance, it would appear that the labels on drugs are surely missing a great deal of relevant information!

Furious Seasons has a long post regarding the psych meds listed in the report, so I won’t steal his thunder except to say that the usual suspects were linked to a large number of deaths. It is important to note that these reported deaths were not necessarily caused by the drug, but that whomever reported the event thought a relationship between death and the drug may exist.

It is a sobering article that really reinforced my curiosity as to what extent we really know about the safety of our medicines. It has previously been investigated thoroughly that clinical trials do a very poor job of reporting safety outcomes, so I suppose the latest study is actually not particularly surprising. For example, as reported in the American Journal of Psychiatry, across a reasonably large sample of psychotropic drug trials:

On average, drug trials devoted one-tenth of a page in their results sections to safety, and 58.3% devoted more space to the names and affiliations of authors than to safety.

Bummer. And, from the Journal of the American Medical Association regarding clinical trials for a wide variety of interventions:

Overall, the median space allocated to safety results was 0.3 page. A similar amount of space was devoted to contributor names and affiliations… Only 39% of trials had adequate reporting of clinical adverse effects and only 29% had adequate reporting of laboratory-determined toxicity.

I’m not trying to instill a panic, but it is at least a little scary that clinical trials don’t provide adequate information and, apparently, the labels of drugs are missing a significant number of relevant adverse drug effects. But hey, what’s a few dead people when there are buckets of money to be made?

Update: John Grohol at Psych Central has some intelligent comments about the Archives of Internal Medicine study, mentioning that we need to know how many people are taking said drugs in order to compare the list adverse events for each drug to the number of people taking each medication. I agree with his comment and also believe that we need to be vigilant -- drug safety reporting is a joke and needs to change.


soulful sepulcher said...

I wrote a long post resulting from the Furious Seasons article too.

Sobering indeed. This is just too painful--these are REAL PEOPLE not numbers, as you and everyone knows--can we all imagine the faces and life stories representing each Clozaril death for example?

I want my daughter to live. Every day I hope she doesn't die, as a result of using a highly toxic and deadly chemical in the name of mental wellness.

Anonymous said...

Well, yes, it would be good to put these numbers into some context, but even if we really knew how many people were taking each of these drugs (and even though prescriptions written are tracked the number of people is not as I understand it anyway) it wouldn't really mean that much since adverse events are so vastly underreported -- some people put the number of reports at 10% of the total, some at only 1%. It's quite possible everyone has some kind of adverse reaction frankly. These drugs are toxic. Whatever way you look at it lots of people seem to be dying on these drugs and maybe proving direct causation isn't easy but there's a lot of circumstantial evidence.

IC said...

When I first read this study, one of the things that immediately caught my attention was the limitation that states that the submission of an adverse event does not establish causality. An adverse drug event could be reported by anyone who felt that there was a relationship between their drug and their adverse event. Right away this signaled to me that more research is needed to be sure that these adverse events are in fact being caused by the prescription drugs. I quickly visited the FDA MedWatch website and noticed how easy it was to submit a report. The reporting system should be altered, so that opinions from second sources such as health care providers can confirm suspected relationship with the drug. I agreed with Furious Seasons’ post that the media and the FDA need to further inform the public about the serious risks their prescription drugs may elicit, but I also feel that it is essential that more research be conducted first. Bringing too much attention to these premature findings could lead many people to feel trepidation when taking their drugs or may lead them to report more and more serious injuries that may not even be related to the drug effects.

CL Psych said...


"Bringing too much attention to these premature findings could lead many people to feel trepidation when taking their drugs or may lead them to report more and more serious injuries that may not even be related to the drug effects."

Interesting point. When taken too far, though, this leads to perpetuating the current system of underreporting adverse events. Of course, if they were reported accurately in clinical trials, that would be a nice start!