May 25, 2012

Cancer Drug Side effects: Are you getting the whole story?

In a word (or two), maybe yes and maybe no.  Lists of side effects are easy to find.  Every drug has them.  These lists may be so long that they become almost meaningless.  As you leaf through these listing, several questions arise: 
1)    Is the list complete? Are there any side effects missing that I need to know about?
2)    Are all these side effects really caused by the drug?
3)    How do I know which of these side effects may happen to me?

How are side effect reported
We will tackle the first two questions, the third deserves its own blog post.  Researchers who study new cancer drugs are the first to report side effects.  Side effects can also be reported to the FDA after a drug is approved and regularly prescribed. Researchers report every adverse event that happens to their patients who are participating in a clinical trial.  Adverse events are reported together with their grade and “relationship to treatment.”  The grade is a measure of severity and for every imaginable adverse event, there is a table that describes what is mild (grade 1), moderate (grade 2), severe (grade 3), and life threatening (grade 4).  Clinic notes in research centers are filled with these mysterious grades whenever anything untoward happens. 

The relationship to treatment is determined by the research physician’s best judgment about whether the adverse event was caused by the drug or not.  There are shades of grey here:  related, probably, possibly, unlikely, and not related.  The decision is basically a judgment call, an educated guess.  Sometimes it’s obvious: you are feeling great and get the flu along with your entire family.  Pretty unlikely the drug had anything to do with it.  Often it is not so obvious.  People with cancer may also have other medical conditions and take many different drugs.  The illness itself takes a toll. When something untoward happens, there are many possible causes. 

With all this reporting, how could side effects go unnoticed?
Rare side effects can, of course, go unnoticed if they didn’t happen during the study.  Sometimes, the source you are relying on (i.e. research paper) listed only a subset of the
side effects.  Some papers list only grade 3 or higher side effects.  That may be fine if you are only interested in the most serious ones, but there are plenty of grade 1 and 2 side effects that can take a real toll on quality of life.  Journal editors sometimes insist, to save space in the pages of journals, that grade 1 and 2 side effects be left out!  Hard to believe, but true.  The side effect table are always much longer when everything is included.  Another way where side effects might be under-reported is if only treatment-related side effects are listed.  Since you care about things that the treatment can cause, this sounds good and it often is, but the relationship to treatment is just an educated guess. Unusual or unexpected side effects might be judged to be unrelated, especially if they are rare and red flags fail to go up.

And how do I know that the side effects are real?
Virtually every drug in the universe “causes” occasional nausea, dizziness, and cough.  Why is that?  It’s because people get nauseated, dizzy, and cough a little quite often.  Yes, there are drugs that can cause these things, but many drugs do not.  These side effects are reported because they happened while someone was taking a drug not because they were taking it.  How can you tell the difference?  If you can find a study of the drug that was randomized and blinded, and half the patients got a placebo, you are just about home free.  Many side effects occur with equally frequency with both treatments and some are more frequent in patients taking the real drug.  These are the true side effects.

The bottom line is that if you need to understand fully what side effects to expect, you will need to look under the hood.  A simple list may not be enough.   The source of the list will need to be examined to understand how likely it is to be complete.  If all the side effects, regardless of grade or relationship, are included, and there is a group of patients getting a placebo in the same study, you stand the best chance of having a complete and accurate sense of the side effects. 

To put a smile on your face see Larry's latest cartoon

(c) 2012 Tom Beer and Larry Axmaker


  1. It seems even within the '4' life threatening catagory, there are distictions. PML (progressive multifocal leukoencephalopathy) is a small but often deadly risk for those taking certain MS drugs, wheras the more serious side effects of ipilimumab are usually treatable when caught early by vigilant trial administrators and patients.

    1. Agree. There are many distinctions and certain rare but serious events that can occur. Thanks for the insightful comment.

  2. Hey, Drugs is always has risk so to use it in even a certain quantity than also it harms the body.

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