Identification of Natural Health Product-Associated Adverse Events and Natural Health Product-Drug Interactions in Adults and Children with Cancer

• Author / Creator

  Bharadia, Morgan K

• Background: Patients with cancer frequently use natural health products (NHPs) to help treat cancer, reduce side effects, or improve effectiveness of conventional cancer treatment, and improve their quality of life. Often oncology healthcare providers do not inquire about NHP use, leading to low rates of disclosure from patients. NHPs are commonly perceived by patients as helpful and safe, with limited recognition of the potential adverse events (AEs) or NHP-drug interactions. However, patients with cancer are susceptible to clinically important AEs and NHP-drug interactions due to the bioactive compounds that NHPs may contain, the narrow therapeutic index of anticancer medications, and polypharmacy. Serious safety concerns also exist because of variations in the quality control of NHPs. We hypothesize that patients with cancer who take NHPs are at a higher risk of experiencing clinically important AEs, including NHP-drug interactions.

  Methods: A two-pronged approach was undertaken. Two systematic reviews were conducted to synthesize the existing clinical evidence on the efficacy and safety of concurrent use of NHPs and anticancer medications. Two anticancer drug categories, immunotherapy and antimicrotubule anticancer agents, and nine clinically relevant NHPs were the focus of these systematic reviews. Findings were presented as a narrative synthesis with summary tables.
  Two cross-sectional studies using Study Of Natural health product Adverse Reactions (SONAR) active surveillance methods were conducted to identify and characterize NHP use, and associated AEs. One study focused on adults with cancer and the other on children with cancer. Patients were asked about their use of NHPs, prescription medications and AE(s) experienced. Those reporting NHP use and a serious AE were provided a consent form for a follow-up interview to inform causality assessment.

  Results: Available clinical evidence on concurrent use of NHPs and anticancer medications identified in the systematic reviews was heterogeneous and primarily consisted of phase I/II clinical trials and pilot studies with methodological limitations as well as case series/reports. Several AEs associated with NHPs were identified including safety signals with the use of vitamins C, D, and E, milk thistle, and turmeric alongside antimicrotubule agents.
  Active surveillance was implemented in Canadian cancer centres as part of routine clinical workflow. Most patients with cancer take NHPs and many take them along with prescription medications. Thirty-seven percent of adults and 31% of children taking at least one prescription medication or NHP reported AE(s). Unexpectedly, the proportion of patients reporting AEs was not significantly different in those taking NHPs and prescription medications concurrently, and those using prescription medications alone. High losses to follow-up occurred prior to causality adjudication.

  Conclusion: This work has expanded our understanding on the safety of NHP use in patients with cancer. Contrary to our hypothesis, and to our surprise, active surveillance did not demonstrate that patients with cancer who take NHPs are at a higher risk of experiencing clinically important AEs. Critical considerations of this work include that each NHP may have differing impacts on AEs, and it is not possible to determine NHP causation of harm using these studies alone. NHP-associated AEs and NHP-drug interactions were identified in our systematic reviews. Although these safety signals are hypothesis generating, as opposed to hypothesis-proving, they are a reminder that NHP use cannot be ignored throughout patient care. Until important research gaps are addressed, recommendations on the use of NHPs in patients with cancer must be individualized; given the seriousness of the condition being treated, continued caution about polypharmacy appears prudent.
  There is a continued need for clinical research with improved reporting of harms outcomes on the use of NHPs and anticancer medications to support clinicians in shared decision making. Causality assessment is also crucial to improve our understanding of the NHP-associated AEs in this population. There are opportunities for enhancement of our active surveillance method by screening only patients being actively treated with anticancer medications, utilizing an electronic screening form, incorporating validated patient-reported AE measurement systems and additional demographic questions, and linking to healthcare databases. Our active surveillance methods can be adopted more widely to be used as a framework for improved inquiry and documentation of NHP use and AEs in routine oncology practice, and to augment pharmacovigilance of NHPs to enhance safety signal detection through the development of a population-based database.

• Subjects / Keywords

  • natural health products
  • pharmacovigilance
  • cancer
  • adverse events
  • interactions

• Graduation date

  Spring 2022

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/r3-12xc-qq32

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.