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. Author manuscript; available in PMC: 2024 Sep 1.
Published in final edited form as: Pediatr Blood Cancer. 2023 Jul 17;70(Suppl 6):e30581. doi: 10.1002/pbc.30581

Children’s Oncology Group’s 2023 Blueprint for research: Pharmacy

Andrew R Ostrenga 1, Jennifer Thackray 2, Ha-Mill H McLearan 3, Kevin M Mulieri 4, Elizabeth Bisaccia 5, Olga Militano 6, L Lee Dupuis 7, M Brooke Bernhardt 8, COG Pharmacy Discipline Steering Committee
PMCID: PMC10529855  NIHMSID: NIHMS1916220  PMID: 37460409

Abstract

Children’s Oncology Group (COG) pharmacists and pharmacy technicians from more than 200 COG-member institutions comprise the COG Pharmacy Discipline. Discipline members serve an essential role in the design and execution of COG clinical trials. Core activities include study drug management, study drug access, clinical trial operations, protocol harmonization, and direct patient care. Discipline members are also actively involved in continuing education, membership engagement, and research across other COG committees/domains. Future areas of committed growth for the Discipline include pharmacogenomics, pharmacokinetics, pharmacoeconomics, pharmaceutics, and implementation science.

Keywords: pharmacy, clinical trials, investigational pharmacy, clinical pharmacy

Introduction

Over 1400 Children’s Oncology Group (COG) pharmacists and pharmacy technicians from more than 200 COG-member hospitals, universities, and cancer centers across 5 countries are members of the Pharmacy Discipline Committee (hereafter, “Discipline”). The Chair and Vice-Chair of the Discipline lead a nine-member Steering Committee that is supported by three subcommittees: 1) Membership Engagement and Communications 2) Continuing Education and 3) Research. The Committee works closely with two COG Clinical Research Pharmacists. The mission of the Discipline is to: 1) set the standard for optimal pharmaceutical care of children, adolescents, and young adults with cancer enrolled on COG clinical trials, 2) meet the unique educational needs of pharmacists providing pharmaceutical care to these patients, and 3) further pediatric oncology pharmacy practice by developing and conducting research within the COG.

Core Activities

Study Drug Management

The Discipline supports institutional compliance with the National Cancer Institute (NCI) requirements for investigational drug handling through the COG Audit Course, answering inquiries from institutions, and developing focused education. The Discipline Chair serves on the Institutional Performance Monitoring Committee and focuses on medication-related issues that may affect data quality. In the future, the Discipline is planning to promote best practices for investigational and oncology pharmacies and create resources specific to pediatric oncology clinical trials management.

Study Drug Access

The Discipline works with the COG Clinical Research Pharmacists to identify new and ongoing medication shortages, assess their impact on patients enrolled in COG trials and develop therapy modifications for communication to COG members. Pediatric cancer therapy is very susceptible to medication shortages due to the high utilization of older and off-patent medications that often have a narrow market. Members of our Discipline have collaborated with others across COG to study the impact of drug shortages and the need for increased focus on ensuring access to essential medicines.1-4 Further, we work with the Food and Drug Administration (FDA), COG leadership, and drug manufacturers to resolve current shortages and prevent future shortages through communication, stock management and importation assistance. Ongoing critical shortages have impacted core medications to treat pediatric cancers, including asparaginase, carboplatin, cisplatin, etoposide, fludarabine, leucovorin, methotrexate and vincristine. The Discipline is planning to collaborate with other stakeholders to develop future strategies for shortage prevention, with ideas such as establishing a national strategic chemotherapy stockpile, exploring expiration date extension and/or additional testing of expired drug supply, and streamlining the medication importation process.

Clinical Trial Operations

The Discipline plays a vital role in the conduct of pediatric oncology clinical trials (See Figure). As medication experts, COG pharmacists ensure trials are conducted safely and effectively in this complex patient population. The Discipline maintains resources such as the Pharmacy Protocol Review Guidelines to support COG pharmacists. The Discipline Chair assigns Pharmacist Liaisons to all Disease and Domain committees. Liaisons apply their expertise and experience to benefit Disease and Domain committees and serve as a line of communication to the Discipline. Liaisons also assign a study pharmacist to all therapeutic and supportive care research protocols. Currently, forty-nine pharmacists are members of the study committees of 79 COG protocols. They participate in protocol development and verify that the pharmaceutical aspects of the protocols adhere to the Pharmacy Protocol Review Guidelines to ensure that protocols, with respect to medication-related issues, are feasible and medications are administered consistently and safely. Specifically, participation of a pharmacist in protocol development facilitates the: 1) ability to implement the treatment plan as described; 2) accuracy of drug information and consistency between all sections of the protocol and COG Chemotherapy Administration Guidelines; 3) adaptation of dose modification recommendations based on the current, published management of adverse effects; 4) implementation of safety standards for the ordering and administration of chemotherapy to reduce risk of potential errors; 5) use of efficient methods of medication preparation and administration to optimize workflow and minimize the cost of therapy; and 6) consideration of pharmacoeconomic aspects of studies, when feasible. For Investigational New Drug (IND) permits held by the COG, the study pharmacist, in collaboration with the COG Clinical Research pharmacists, provides estimates and updated projections of study drug needs for trial completion.

Figure.

Figure

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Pharmacy Discipline impact on Children’s Oncology Group (COG) clinical trials.

Pharmacist study committee members also answer medication-related questions during the conduct of the study. Like other study committee members, pharmacists take an active role in data analysis, interpretation of study results and manuscript development. When medications that require complex delivery or monitoring are introduced into COG protocols, Discipline leadership and study pharmacists collaborate with the study sponsor, to develop appropriate procedure and educational materials to ensure that medications are stored, prepared, and administered appropriately. This includes information regarding medications that require complex calculations, manipulations, or specialized handling. Members of the Discipline have a long-standing relationship with Nursing Discipline members and have shared our efforts externally to help generalize study-related knowledge for general patient care.5 Finally, the Discipline has collaborated with study sponsors to develop protocol information and provide solutions for patients who are unable to swallow oral solid dosage forms or cannot tolerate medication excipients.6

Protocol Harmonization

Discipline members participate in COG efforts to harmonize protocols across disease states and committees to standardize chemotherapy and supportive care where feasible with the goal of optimizing patient care, minimizing the risk of medication errors, and establishing a treatment standard upon which clinical trials can be designed. Discipline members played an active role in the Chemotherapy Standardization Task Force that developed Solid Tumor and Leukemia Lymphoma Chemotherapy Guidelines and in COG-led efforts to harmonize complex dosing of carboplatin.7,8 These guidelines pioneered the development of infant dosing tables that parallel a gradual transition from historic weight-based dosing (mg/kg) to body surface area based dosing (mg/meter squared) to ensure medications are appropriately dosed on the patient’s size while avoiding significant dose adjustments due to slight age, length, or weight changes. Discipline members collaborate with the COG Clinical Research Pharmacists to maintain the Commercial Agents Monographs, Chemotherapy Administration Guidelines, and Extravasation Guidelines that provide important information underpinning study protocols. These activities streamline protocol development and prevent confusing inconsistencies between protocols.

Direct Patient Care

COG Pharmacists educate patients enrolled on COG studies and their caregivers regarding the appropriate use of medications. Pharmacists are well-recognized as experts in pharmacology, optimizing medication formulations, and age appropriate teaching/training. In many sub-specialties, pharmacists are routinely engaged as an essential member of the interprofessional team and are charged with educating patients/caregivers and optimizing medication adherence, health literacy, and medication-related outcomes. This is an area of practice for many of our members and one in which we hope to demonstrate our role in future COG trials.

Pharmacy Discipline Subcommittees

Membership Engagement and Communication (MEC) Subcommittee

Created in 2020, the MEC Subcommittee (20 members) addresses the evolving educational, professional, and networking needs of our pharmacist members related to the Discipline’s core activities. Quarterly electronic newsletters and quarterly webinars are employed as vehicles to promote member engagement and communication. The concept, design, organization, and dissemination of both vehicles are overseen by the MEC Subcommittee and the Discipline Steering Committee. Discipline members have expressed strong satisfaction with both the newsletters and webinars. In 2022, 430 members attended at least one of the four webinars offered throughout the year.

In 2022, the MEC Subcommittee conducted a survey of the Discipline membership to garner input on prioritization of educational initiatives and identify opportunities for further member engagement. The majority of respondents expressed involvement (180/182, 99%) in core Discipline activities; however, a smaller number reported awareness of current resources and networking opportunities (144/182, 79%) provided by the Discipline. Respondents provided feedback that is being used to plan future Discipline activities. Most respondents expressed interest in additional opportunities to network with other COG Pharmacists, and in additional education opportunities on the topic of COG operations. In addition, 1/3 of respondents took the opportunity to volunteer to join a Discipline subcommittee or participate in a Discipline activity. Based on the survey results, the MEC is planning future collaborative endeavors to support COG Pharmacists.

Continuing Education (CE) Subcommittee

The primary venue for CE provision to COG pharmacists is the Betsy Poon Pharmacy Education Series. Named after the previous Discipline Chair, this program is offered at the COG Fall Meeting and has grown significantly since its inception in 2014. In planning the Betsy Poon Educational Series, the CE Subcommittee completes educational needs assessments, selects program topics and speakers, develops learning objectives, and assists with grants and fundraising. Pharmacist CE opportunities have grown considerably under the Subcommittee’s oversight. Initially, 1 hour of in-person CE was offered. In contrast, 5.75 hours of in-person and live-streamed programming was provided at the 2022 COG Fall Meeting. The 2023 COG Fall Meeting will include the 10th CE series provided by this subcommittee. The committee hopes to continue to expand future educational offerings to include interprofessional programming and enduring continuing education for members unable to attend the live meeting.

Research Subcommittee

The mission of the Pharmacy Research Subcommittee is to strengthen the ability of our members to perform research as well as developing study aims that enhance COG protocols. Conducting research as an individual at a single institution can pose challenges regarding access to trained pharmacy mentors, obtaining cross-discipline collaborators, and uncertainty around how to initiate, conduct, and complete a quality research project. As such, the Discipline established a Research Scholar Program for COG pharmacists seeking support to start and grow their research experience and portfolio. The COG Pharmacy Scholar Program aims to foster pharmacist-initiated research that addresses the mission of the COG by linking a promising pharmacist with a mentor to perform a research project. The COG Pharmacy Research Subcommittee acts in an advisory capacity for the program.

Through the Pharmacy Scholar Program, the Discipline successfully performed stability research in extemporaneously prepared medications. An example of this includes stability of extemporaneously compounded temozolomide suspension published by Lingert-Walsh et al in the Journal of Oncology Pharmacy Practice in 2021.9

In addition, Pharmacy Research Subcommittee members review submissions to the annual COG Fall Meeting Pharmacy Poster Session. The submitted abstracts are scored and those that score well are invited to deliver an oral presentation at the annual COG Fall Meeting. The poster session and oral presentations provide an opportunity for COG Pharmacists to share their research with other members of the Discipline and develop collaborations.

Contributions to COG Scientific Output/Publications

COG Pharmacists serving on numerous study committees have contributed to study activities including study design, protocol development, analysis of data, and contributions to the final manuscript. Among some of the more recent examples include publications stemming from the following trials: ADVL1211, AALL0434, AALL1331, AALL1621, ANBL12P1, and ARST1321.10-16

Future Activities

The Discipline is continuing to explore opportunities to contribute to COG clinical trials and collaborate with other COG committees. Recently, the Discipline formed a Pharmacogenomics Subcommittee to focus on this rapidly developing area of pediatric oncology research and patient care. Discipline members have been actively engaged in pharmacogenomic research, in some cases as a secondary aim of a COG trial.17-20 This subcommittee is planning to formalize and expand these efforts. Short-term goals include updating the COG Commercial Agent Monographs by adding a pharmacogenomic section where evidence exists and creating a COG resource document that will address pharmacogenomics of supportive care and antineoplastic agents to inform COG protocols. In collaboration with other COG Committees (e.g., Epidemiology Domain), the Pharmacogenomics Subcommittee will develop study concepts to investigate the impact of pharmacogenomic variants on drug disposition, toxicity, and efficacy using data from Project:EveryChild (APEC14B1, NCT02402244) and the NCI Molecular Characterization Initiative.

Long-term goals include incorporating pharmacogenomic testing into COG protocols to study the influence of germline variation on clinical outcomes. We believe the data generated will be used to decrease on-treatment toxicity, improve treatment-related survival, and mitigate health disparities among patients on trials.

The Discipline also aims to lead and participate in study aims and trials in pharmacoeconomics, pharmacokinetics, and pharmaceutics/drug delivery. It is critical to understand and exploit data from these fields to assist therapeutic decision-making. Pharmacoeconomics and health economics can inform how to best prioritize treatment approaches for patients of varied personal and financial circumstances. Pediatric oncology includes a wide array of patient populations from neonates to adolescents and young adults. Pharmacokinetic research of both novel and existing therapeutics can help better describe differences among patients across the age spectrum. Increasing our understanding of the impact of obesity on pharmacokinetics and pharmacodynamics is a critical need in our field. We have expertise within our Discipline which can be leveraged to explore these critical issues in further studies.20

Pharmaceutics/drug delivery research can improve clinical trials and implementation of study results by ensuring that medications to treat pediatric cancers can be safely and effectively delivered both in the hospital as well as in the home. We have the needed expertise within our Discipline, and it is a high priority to continue to study these questions across populations.21

Finally, COG pharmacists are essential to ensuring appropriate translation of the study protocol in their institutions to the bedside – both during the trial and when study procedures become part of routine clinical care. Adherence to supportive care guidelines is not universally successful, as members of our Discipline and others within COG have noted.22 We are exploring opportunities for the Discipline and its members to become more actively engaged in implementation science approaches to optimize adherence to on-study procedures and supportive care guidelines.

Conclusion

The core activities of the Discipline are integral to COG trial operations and the production of high-quality research data. The Discipline Steering Committee’s focused efforts on member engagement, communication, education, and research ensure COG Pharmacists are supported in their clinical practice and remain connected to others who practice in this sub-specialty. Future areas of research within the Discipline, such as pharmacogenomics, will seek to optimize patient and system outcomes of current and future therapy.

Funding support:

Grant support from the National Institute of Health, U10CA180886, U10CA180899.

Abbreviations Key

CE

Continuing Education

COG

Children’s Oncology Group

FDA

United States Food and Drug Administration

IND

Investigational New Drug

NCI

National Cancer Institute

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