Improving safe off-label uses of medications

Assessment Questions

  1. Which of the below statements best describe an adverse drug reaction?
  1. A response to a drug which is noxious and unintended, occurring at normal doses used in humans
  2. An effect that occurs with the desired effect of a medication that is usually unwanted and can be harmful.
  3. An event that is considered a failure in the medication treatment A failure in the treatment course that leads to or could lead to patient harm.
  4. A situation where a medication affects the activity or concentration of another medication when they are given together

Correct Answer: A

Explanation of answers:

  1. Definition of an adverse drug event
  2. Definition of a side effect
  3. Definition of a medication error
  4. Definition of a drug interaction
  1. The identification of adverse drug reactions is best conducted through:
  2. Review of voluntary reporting
  3. Retrospective chart review
  4. Prospective active surveillance
  5. A combination of active surveillance and chart review

Correct Answer: D

Explanation of answers:

Voluntary reporting is one method for identifying adverse drug reactions. However, the number of events reported is highly under representative of the true number of events that occur. Retrospective chart review is another method to detect adverse drug reactions. Unfortunately, due to the retrospective nature of this method, many times there is a lack of needed information to assess the temporal relationship of the event to medication administration or initiation. Adverse drug reactions are also not always documented in the patient chart. Prospective active surveillance allows the identification of adverse drug reactions in real time and provides information of temporal association and the severity of the outcome. However, some events may be missed to the lack of continual presence of the investigator. A combination of prospective evaluation and chart review provides two modes of adverse drug reaction identification with the benefits of both described above.

  1. According to The Omnibus Budget Reconciliation Act of 1990, which of the following is not a resource to support a medically acceptable indication?
  2. The American Hospital Formulary Service Drug Information
  3. The American Medical Association Drug Evaluations
  4. The United Stated Pharmacopoeia-Drug Information
  5. Informational advertisement in a non-scientific magazine

Correct Answer: D

Explanation of answers:

The Omnibus Budget Reconciliation Act of 1990 lists, The American Hospital Formulary Service Drug Information, The American Medical Association Drug Evaluations, and The United Stated Pharmacopoeia-Drug Information as compendia that could be used when determining if a medication id being used for a medically acceptable indication. Therefore, answers a, b, and c are correct. Answer d is incorrect and the clinician should keep in mind that scientifically sound evidence should accompany the use of off label medications.

  1. The informed consent process should be conducted when a medication is being used for an investigational indication. Which of the below statements include a component of the informed consent process?
  2. Ask a family member to sign the consent form if the patient, who is deemed competent, is out of the room.
  3. Ask the patient to sign the consent form without reading the details of the study.
  4. Inform the patient that this is research and participation is voluntary
  5. Inform the patient that this is part of patient care

Correct Answer: C

Explanation of answers:

The patient should be assessed for competence of providing informed consent. If the patient is deemed competent, they are the individual that should be approached concerning the informed consent. The patient should also be aware of the details of the study and sign the consent form only after their questions are answered and they understand the document. The patient also needs to be informed about the nature of the study, including a clear explanation that participation is voluntary, as it is a research study and not usual patient care.

  1. Which of the below statements are true regarding future research that needs to be conducted in regards to the evaluation of the safety of off-label medication use?
  2. Investigations utilizing voluntary reporting data of ADRs
  3. Investigations with standardized definitions of ADRs
  4. Investigations with extensive exclusion criteria
  5. Investigations focused on the cost of off-label use

Correct Answer: B

Explanation of answers:

To best capture adverse drug reactions, clinicians should not solely rely on voluntary reporting as this method of adverse drug reaction detection underrepresents the true incidence of adverse drug reactions. Including a standardized definition of when an event is considered an adverse drug reaction assists the readers in understanding the criteria used to evaluate the association between an event and a medication. Consistent definitions of adverse drug reactions between studies would be additionally beneficial in the evaluation of the safety associated with off-label medication use. Through the expansion of exclusion criteria in clinical trials, additional subpopulations are not studied, which would not begin to solve the problem of the scarcity of evidence to support the off-label use of some medications in subpopulations. While the cost of off-label use is an important aspect to consider, this question specifically asks about research to assist in the evaluation of the safety of off-label use.