Preemptive pharmacogenetic testing to guide chemotherapy dosing in patients with gastrointestinal malignancies: a qualitative study of barriers to implementation

Abstract

Background Pharmacogenetic (PGx) testing for germline variants in the DPYD and UGT1A1 genes can be used to guide fluoropyrimidine and irinotecan dosing, respectively. Despite the known association between PGx variants and chemotherapy toxicity, preemptive testing prior to chemotherapy initiation is rarely performed in routine practice. Methods We conducted a qualitative study of oncology clinicians to identify barriers to using preemptive PGx testing to guide chemotherapy dosing in patients with gastrointestinal malignancies. Each participant completed a semi-structured interview informed by the Consolidated Framework for Implementation Research (CFIR). Interviews were analyzed using an inductive content analysis approach. Results Participants included sixteen medical oncologists and nine oncology pharmacists from one academic medical center and two community hospitals in Pennsylvania. Barriers to the use of preemptive PGx testing to guide chemotherapy dosing mapped to four CFIR domains: intervention characteristics, outer setting, inner setting, and characteristics of individuals. The most prominent themes included 1) a limited evidence base, 2) a cumbersome and lengthy testing process, and 3) a lack of insurance coverage for preemptive PGx testing. Additional barriers included clinician lack of knowledge, difficulty remembering to order PGx testing for eligible patients, challenges with PGx test interpretation, a questionable impact of preemptive PGx testing on clinical care, and a lack of alternative therapeutic options for some patients found to have actionable PGx variants. Conclusions Successful adoption of preemptive PGx-guided chemotherapy dosing in patients with gastrointestinal malignancies will require a multifaceted effort to demonstrate clinical effectiveness while addressing the contextual factors identified in this study.

Implementing Pharmacogenetic Testing in Gastrointestinal Cancers (IMPACT-GI): Study Protocol for a Pragmatic Implementation Trial for Establishing DPYD and UGT1A1 Screening to Guide Chemotherapy Dosing

“…We established implementation in one service line (GI oncology) to build necessary clinical operations to deliver PGx testing. Conducting qualitative interviews during the Exploration phase were vital in identifying barriers to implementation and at the same time provided an opportunity to engage and educate key personnel about the intervention ( 30 ).…”

“…A brief survey was distributed during the interview to collect participant demographics and quantitatively assess level of comfort in interpreting PGx results. Barriers to testing highlighted by our clinicians included a limited evidence base and burdensome workflows related to testing (e.g., lengthy turnaround time, financial concerns, EHR integration); full results of this study are published in a separate manuscript ( 30 ). Our qualitative study allowed us to identify contextual factors deemed essential to test uptake within our institution and refine strategies to address barriers during the implementation study.…”

Assessment of the Clinical Utility of PretreatmentDPYDTesting for Patients Receiving Fluoropyrimidine Chemotherapy

“…The lack of recommendation from clinical practice guidelines is a major reason medical oncologists in the United States do not order pretreatment DPYD testing. 39,40 Therefore, it is critical to understand why clinical guidelines committees have not recommended testing and what evidence is needed to demonstrate clinical utility. The cochairs of the NCCN Guidelines for Treatment of Colon Cancer recently explained their committee's lack of endorsement.…”

“…Finally, pragmatic implementation studies (eg, Clinical-Trials.gov identifier: NCT04736472) will provide additional information about the facilitators and barriers to implementation and help develop best practices for integrating pretreatment DPYD testing into clinical workflows. 39,40 A comprehensive discussion of the critical implementation issues, including test availability, selection, ordering, cost, turnaround time, interpretation, and reimbursement, is beyond the scope of this article, but some of these issues have been recently reviewed generally for GITR/ pharmacogenetics 65 and specifically for DPYD. 45 In conclusion, FP dose reduction in DPYD carriers normalizes their systemic FU exposure and toxicity with WT patients receiving SOC doses.…”

Opportunities for personalizing colorectal cancer care: an analysis of SEER-medicare data

“…Implementing these guidelines into clinical practice has been limited by questions around cost of testing, magnitude of impact, insurance reimbursement, and unclear clinical actionability. ( 18 – 22 )…”