Off Label Prescriptions Risk More Adverse Drug Effects Interview with:
Tewodros Eguale, MD, PhD
Department of Epidemiology, Biostatistics, and Occupational Health,
McGill University, Montreal, Quebec, Canada
Research Fellow in Medicine
Brigham and Women’s Hospital

Medical Research: What is the background for this study?

Dr. EgualeOff-label prescribing is common and has been identified as a potentially important contributor to preventable adverse drug events (ADE). Significant deleterious effects were reported with off-label use of some drugs. Moreover, studies in children, where drugs are often used without sufficient scientific investigation, have shown that off-label uses increase the risk of ADE.  In adults, there has been no systematic investigation of the effects of off-label use in real world situation. The lack of knowledge is related to the methodological challenges of measuring off-label use and its effects; specifically the lack of link between prescribed drugs and their indication for use. The Medical Office of the XXI Century (MOXXI) electronic health record (EHR), developed by team of researchers at McGill University, facilitates the documentation of treatment indications, reasons for discontinuation of drug orders and adverse drug event. These new features provided the first opportunity to systematically monitor and evaluate off-label use and the occurrence of adverse drug events.  This study took advantage of the use of this new generation of software in a network of primary care practices to systematicaly evaluate the effect of off-label use on ADEs.

Medical Research: What are the main findings?

Dr. Eguale: We evaluated 151,305 prescriptions written for 46,021 patients and found out that off-label use was 11.8%, of that, off-label uses which lacked strong scientific evidence constitute 80.9% (4 in 5). In general, off-label use increased the risk of ADE by 44% compared to on-label use and off-label use which lack strong scientific evidence increased the risk of ADE by 54%. In addition, we found that the risk of ADE for off-label uses with strong scientific evidence was the same as on-label uses. These findings were adjusted for important patient-level and drug-level confounders including patient age, sex, Charlson comorbidity index, number of drugs the patients was taking, drug class and drug age.

Medical Research: What should clinicians and patients take away from your report?

Dr. Eguale:

Our study demonstrated that physicians need to be cautious in prescribing off-label when there is a lack of strong scientific evidence for the use of a drug for a particular treatment indication. Physicians have to educate themselves or be equipped with computerized decision support systems to identify drugs and their approved and off-label indications and the scientific evidence associated with off-label uses.  In situation where off-label use is necessary, physicians should inform their patients and be more vigilant in identifying adverse drug events early to ameliorate their effect. For patients, there needs to be a dialogue with their prescribers as to ‘why a drug is prescribed’ and the possible alternatives available to treat the condition (other drugs and non-drug treatments) before taking off-label drugs.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Eguale:

  1. This study is possible due to active participation of physicians. Documentation of treatment indication and treatment outcomes in EHR are value-added features for the physicians, which facilitated the creation of a ‘problem list’ of active and current diagnoses as well as allowing automated check for drug-disease interactions. Documentation of treatment outcomes with the treatment indication help to create ‘drug treatment histories’ in EHR. These electronic health record features could be incorporated in any other EHR. Our study demonstrated that EHR implementation would be greatly aided if clinically relevant features are added to electronic systems.
  1. The treatment indication and whether the drug is approved by regulatory bodies should also be communicated to the patient in plain language (e.g, not as ‘hypertension’, but as ‘high blood pressure’, even better as ‘to decrease blood pressure and to decrease the chance of heart attack). This will empower patients to evaluate the benefit of the treatment and may help them adhere to the drug treatment. In addition, the treatment indication should be communicated to the pharmacist. This will facilitate communication with patients and aid in discussion of off-label use and help in ‘targeted counselling’ of patients. In addition, having treatment indication will help pharmacists to identify medication errors easily (e.g. wrong drug, wrong dose, look-alike-sound-alike drugs), facilitate medication reconciliation and facilitate communication with care team.
  1. We believe drug regulatory bodies such as US FDA and Health Canada need to monitor off-label use as they are moving towards a progressive drug licensing framework. A new paradigm of drug approval is the reality, where new drugs get earlier market access with the potential for more drug safety problems and off-label use. As a result, we need to strengthen post-marketing of drugs with innovative methods as demonstrated with this publication.
  1. We also believe there is a need to study drugs predominantly used to treat off-label conditions in large randomized control trials to determine their safety and efficacy related to the off-label conditions. The pharmaceutical industry, researchers, consumer groups and governments need to come together to investigate the value of these drugs.


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Tewodros Eguale, MD, PhD (2015). Off Label Prescriptions Risk More Adverse Drug Effects