Off-Label Prescribing Enhanced by Patient-Reported Outcomes

Karen Lee Richards Health Guide
  • I recently came across a rather unusual, but quite interesting study that looked at the PatientsLikeMe Web site and analyzed how the information reported by patients on the site could be a useful tool for both doctors and their patients when it comes to prescribing medications off-label. 

    Identifying the Problem

    Although off-label prescribing may sound like a somewhat questionable activity, it is actually a legal and common practice in the U.S.  When a pharmaceutical manufacturer develops a new drug for a particular purpose, the FDA evaluates the medication's efficacy for that specified purpose.  However, once the drug has been approved and is on the market, physicians are free to prescribe the medication as they see fit, whether it is for the FDA-approved purpose or any other purpose.  In fact, it is estimated that 21% of all prescriptions are given for off-label purposes. 

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    The reason pharmaceutical companies often don't seek FDA approval for multiple purposes is that it takes several years and costs millions of dollars to conduct all of the clinical trials required for each new indication they want to add.  And once a drug goes generic, there is little financial motivation to put that much time an effort into adding another purpose for the medication. 

    Antidepressants and anticonvulsants are two examples of drugs that are often prescribed off-label for certain chronic pain conditions.  The mechanism by which certain drugs in those categories work to relieve depression or prevent seizures can also be effective in relieving pain. 

    The practice of off-label prescribing has its pros and cons:

    • Pros:  Some conditions (like ME/CFS) have no FDA-approved drugs so the only medications that can be used for treating its symptoms must be prescribed off-label.  Even if a condition has one or more approved medications, they may only treat certain symptoms, while an off-label drug might help improve other symptoms.  Also, patients are different and for some the approved drugs may not be effective, making it necessary to try other off-label medications.

    • Cons:   Often there is little scientific evidence underlying the use of a particular drug for a non-approved purpose.  Prescribing a medication based only on anecdotal information or small studies can be risky for patients.  An example cited by the study authors: “In the past, millions of women received prophylactic hormone treatment for the prevention of osteoporosis...However, systematic evaluation revealed no therapeutic benefit and elevated risks of cardiac damage.” 

    Purpose of the Study

    In an effort to identify an additional tool that could supplement traditional clinical trials and enhance the understanding of how medications and other medical products perform once they are actually on the market and used by a wide variety of patients, researchers evaluated the PatientsLikeMe Web site.

    As described in the journal article, “PatientsLikeMe is a web-based community and research platform where patient members share details about their treatments, symptoms, and conditions, with the intention of improving their outcomes. Patients join communities designed specifically for their condition. At the time of writing, there were 11 distinct patient communities and over 70,000 patient members. The site synthesizes members’ data into interactive reports for review. Each member sees a graphical representation of their own and others’ function, treatments, and symptoms over time and can view reports of aggregated data. The site includes an interactive treatment report for each medication and intervention that patients add to the system. The report includes dosages taken, time on treatment, and evaluations of the treatment, including perceived efficacy, side effects, and burden. These treatment reports can suggest usage patterns and effectiveness rates for drugs across different purposes.”

  • The purpose of this study was to see if this tool may aid in evaluating the effectiveness and safety of some treatments more efficiently and over a longer period of time course than is feasible through traditional trials.

    Study Design and Results

    For the purposes of the study, researchers examined patient data for two medications that are widely prescribed off-label and currently being evaluated for new applications: amitriptyline and modafinil (Provigil).  Both of these drugs have frequently been prescribed off-label for fibromyalgia, ME/CFS and other chronic pain conditions. 

    There were 1,948 treatment histories for modafinil and 1,394 treatment reports for amitriptyline reported across five PatientsLikeMe communities: multiple sclerosis, Parkinson's disease, mood conditions, fibromyalgia/chronic fatigue syndrome, and amyotrophic lateral sclerosis (ALS).  A few of the interesting statistics derived from the study include:

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    • The majority of members reported taking the drugs for off-label uses.

    • Only 34 of the 1,755 (1%) reporting purpose used modafinil for an approved purpose – narcolepsy or sleep apnea.

    • Only 104 out of 1,197 members (9%) reported taking amitriptyline for its approved indication – depression.

    • Members taking amitriptyline for off-label purposes rated the drug as more effective than those who were taking it for its approved indication.

    • Sometimes medications are prescribed off-label because of their side effects.  For example, while dry mouth is a commonly reported side effect of amitriptyline for most patients, 88 of 220 (40%) of people with ALS on the drug reported taking advantage of this side effect to treat their symptom of excess saliva.  And 321 of 1197 (27%) patients with insomnia or other sleep problems report taking amitriptyline for it side effect of sleepiness. 

    The researchers concluded, “Patient-reported outcomes, like those entered within PatientsLikeMe, offer a unique real-time approach to understand utilization and performance of treatments across many conditions.  These patient-reported data can provide a new source of evidence about secondary uses and potentially identify targets for treatments to be studied systematically in traditional efficacy trials.”

    My Thoughts...

    While off-label prescribing decisions certainly cannot be made soley based on self-reports of patients in an online community, I think this new tool could add an important and informative new dimension as patients and doctors work together to find the most effective treatments.  Personally, I'm planning to participate in the site and will let you know more about it after I have used it myself.  At the very least, I think it will help me make decisions about treatment options I may be considering because I can see how other patients with the same condition have responded to those treatments. 

    Note:  If you're interested in participating on the PatientsLikeMe Web site, you'll have to wait a few weeks as they are updating the site and testing new features.  During that time, only current members can interactively take part on the site.  You can, however, browse the site, look at some of the reports and get a general feel for what it's all about.  If you're interested in joining, there is a link on the homepage where you can sign up to be notified when the site is accepting new members again. 

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    Frost J, Okun S, Vaughan T, Heywood J, Wicks P. Patient-reported Outcomes as a Source of Evidence in Off-Label Prescribing: Analysis of Data From PatientsLikeMe. J Med Internet Res 2011;13(1):e6.


Published On: February 28, 2011