No Longer The Wild, Wild, West – Advancing on a New Frontier

Advancing research pharmacy is essential in today’s clinical research landscape, where technology and collaboration reshape industry practices. Clinical research is undergoing a transformative period, influenced by emerging technology, new therapeutic modalities, and enhanced knowledge of statistical modeling and biomarkers, necessitating innovations in study designs and increased access to clinical trial treatments.

With this, the overall roles and responsibilities of the research pharmacy have shifted. Once dwelling in a basement (typically), sheltered by stacks of paper, shelves of binders, a computer screen painted with Post-its, and bins of drugs, modern advancements have moved the research pharmacy into a pivotal position, acting not only as drug dispenser and preparer, but now a key department at the center of research operations.

At the recent Research Pharmacy Summit, a core theme of educational sessions and participant dialogue spoke to increased operational complexity, integration of not only technology, but entire departments, and new avenues of communication and collaboration. It was a true testament to the unification and growth of the specialty practice.

In my first days in the IDS service, my mentor once pinned our seemingly disparate and “lawless” operations as “cowboy medicine,” plagued with variable practice amongst research groups, little advanced notification/preparation (…never invited to the SIV!), where we frequently acted in rapid response, rather than out of our SOPs.

Hello 2024. With consensus organizations and new guidelines prompting connection, standardization, and alignment of best practices through policy and procedure development, those days are far behind us. Technology beyond the fax machine and telephone streamline communication and collaboration instantaneously. Electronic health records, accountability systems, and document platforms provide real-time access and transparency to protocols, patients, and data. With this, pharmacy is now free to participate in a new frontier, encompassing novel areas where the practice has shifted to bring the unique perspective and expertise of pharmacy into aspects of clinical trial management. This blog will highlight these areas and discuss the role and impact an IDS practitioner can play.

The IDS team can play an important role in clinical trial activation and aid in accelerating start-up times. Long activation timelines delay the availability of innovative therapy to sick patients and has additional downstream effects on participant accrual rates, impacting overall study success. Delays or unstandardized processes for activation can snowball into longer timelines, with the dynamic nature of clinical trials rendering new amendments requiring further evaluation and updates.

Document Review

To start, the IDS will do a thorough review of initial protocol documents to ensure there are no outstanding barriers to start-up, and that all required documents (such as the pharmacy manual, IB and MSD) are all available to perform a feasibility review. As amendments come up during this time, prompt reviews and responses to any changes or additions can be made. In some practices, the IDS may serve as members on the Scientific Review Committee and or an Operational Review Committee.

Drug Supply & Procurement

As experts in drug therapy, the IDS can determine which drugs are required for the study and how these drugs will be procured. For example, if commercial drugs are required, the IDS can evaluate options for invoicing, such as patient’s insurance, sponsor’s supply or purchasing and reimbursement.

Budget

In addition to evaluating drug supply and handling, the IDS has an important voice in the study budget. IDS fees should appropriately reflect the complexity of the protocol and specific requirements to meet the time and effort of the pharmacy, justifying value and service.  Modification to the budget may be required for substantial protocol updates that impact pharmacy’s operations.

EMR Order Builds

With the transition to electronic orders in the EMR, the IDS team is critical for creating and maintaining investigational drug and order builds. As the primary drug experts, the IDS provides appropriate dosing, timing, and directions for preparation. Direct collaboration with IT analysts, or dedicated pharmacy analyst roles, is required, as well as maintaining appropriate timelines and priority levels for EMR build requests, as this is often a rate-limiting step in study start-up.

EMR drug and order builds are part of the larger Treatment Plan, which provides more extensive details of the protocol regimen, such as concomitant pre-meds, rescue medications, and lab draws. The IDS will review and provide feedback on treatment plans in collaboration with the study team. Finally, once the treatment plan is created, the IDS is involved in a final review, testing, and sign off order before it moves into live production.

Electronic Accountability System Set-up

Coinciding with the EMR order builds, appropriate protocol set-up and building of drugs and orders within the electronic accountability platform is an essential task for performing drug receipt, dispensing, and inventory management. As amendments are approved, builds may need to be updated to account for any significant changes.

Internal Education & Training

For appropriate protocol conduct, the IDS will prepare items such as a pharmacy summit sheet, oral monographic, and drug preparation instructions. Sites may vary in these exact requirements and often follow a template to maintain standardization and ease of use.

In preparation for the study activation, IDS must ensure all team members are trained, and prepare for satellite sites or off-hours, if needed. Documentation on training within an electronic accountability system, CTMS, LMS, or other eSolution ensures all team members are ready.

Updates to these internal training documents, EMR Order builds, and electronic accountability builds, are a continuous responsibility, as amendments are released. Appropriate training must be documented on logs to ensure adequate version control.

Dosing & Order Review

Select practice models support pharmacist-led dosing and clinical review for appropriateness of treatment. This can improve dosing accuracy and result in fewer physician-entered orders necessitating modification or revision, streamlining workflows and avoiding delays in care.  With expertise and attention to patient’s medication history and concomitant therapy, potential drug-drug interactions can be proactively addressed. Pharmacists are in a prime position to examine lab results and intervene when treatment adjustments are necessary.

Phase I/II Pharmacist (Clinical Trial Unit Specialist)

Novel clinical designs for phase I trials have significantly evolved to enhance the accuracy and efficiency of identifying the maximum tolerated dose (MTD) of new drugs. Traditional designs like the 3+3 method, while simple, often fall short in precision. In contrast, modern approaches such as model-based designs (e.g., continual reassessment method) and model-assisted designs (e.g., Bayesian optimal interval and Keyboard designs) offer improved performance. These innovative designs leverage statistical models and historical data to dynamically adjust dosing, thereby optimizing patient safety and trial outcomes. In adaptive platform trials, multiple treatments are evaluated simultaneously against a common control group, and the trial design can be modified based on interim results³. This flexibility allows for the addition or removal of treatment arms, optimizing the allocation of resources and potentially accelerating the identification of effective therapies⁴. Essentially, an adaptive platform trial can be thought of as several studies rolled into one!

These new trial designs aim to improve the precision and speed of clinical research, ultimately enhancing the development of new treatments while ensuring patient safety. However, the complexity and operational challenges such as limited enrollment slots, undefined dose levels, and frequent amendments to critical elements, may necessitate a dedicated pharmacist to manage these studies.

Patient Counseling

Expansion into clinical services allows the IDS to interact directly with patients by providing counseling and education on research medications. IDS Pharmacists are in a unique position to monitor a patient’s adherence to investigational studies due to requirements that dispensed medication be returned and accounted for.  Within certain electronic accountability platforms, settings can prompt an overdue patient return, improving data and compliance. Features of electronic accountability systems, such as alerts, can also improve the tracking of patient returns, timely data reconciliation and improve data integrity during analysis.

Pharmacist-led counseling has an overall benefit in improving medication adherence, increasing patient’s understanding of their therapy and overall experience, along with reducing hospital admissions.^5,6,7

Successful counseling initiatives identify a subset or schedule where benefit may be most realized, such as Day 1 of each cycle for oral chemotherapeutics.

Technology Process Leader

If you’ve practiced in IDS long enough to know the evolution of our favorite acronyms – IVRS, IWRS, IXRS, and now RTSM, then you’ll certainly agree that IDS practitioners are technologically savvy and adaptable. Experienced in the utilization of multiple sponsor-required platforms for training and inventory management, IDS practitioners have key insight into technology and electronic workflow management and can act as process leaders and change champions.

As sites implement new electronic systems, IDS practitioners play a valuable role in the integration and adoption of new workflows that sync sources and departments. A key example is bridging regulatory aspects of protocol management, new patient enrollment or unenrollment, within a Clinical Trial Management System (CTMS). Through interfacing and integration of multiple systems, alignment with one source of truth eliminates duplicative data entry and improves efficiency and timely communication amongst different departments.

Institutional Review Board (IRB) Member

IDS Practitioners may serve as scientific members of the IRB. With expertise ensuring investigational drug are used safely and effectively, an investigational pharmacist plays a crucial role in the IRB. They can provide a thorough protocol review, specializing in the appropriateness of drug doses, routes of administration, and drug-drug interactions. Furthermore, equipped with knowledge of standard of care regimens, pharmacists can offer recommendations on supportive care and safety.  With significant experience analyzing medical information and literature, they can provide input on aspects such as trial design and ethical aspects.

Internal Policy & Procedures Development

Establishment of department policy and procedures, with subsequent standard operation practices (SOPs) is critical to running an effective and uniform service. Three key guidelines, each with a slightly different focus, provide consensus recommendations to support best practice standards.^8,9,10

Notably, site-specific policies should address the following areas:

1. Drug accountability
2. Drug Destruction
3. Document Management
4. Temperature Excursion
5. Monitoring Visits

The IDS plays an active role in developing, maintaining, and enforcing these policies and processes.  As standardized workflows are established, operational efficiency and safety are optimized. To foster collaboration and practice alignment, participation in professional organizations is now an integral component to continued growth and innovation.

Traditional quantitative metrics, such as number of active protocols or the number of dispenses, do not accurately account for clinical trial complexities and the evolving landscape of IDS workload and responsibilities. For example, an adaptive platform study may have 15 amendments, compared with a traditional protocol that has only 3!² Capturing time-based metrics on daily activities, such as shipment receipts, dispensing, IP preparation, and monitoring visits, allows for internal and external benchmarking, productivity assessment, and support staff and resource allocation.

Analysis of protocol elements and requirements can be performed to further describe the operational efforts of the IDS. The Complexity Scoring Assessment (CSA) is a systematic tool developed by the Vizient Pharmacy Research IDS Subcommittee.¹¹ By categorizing trial complexity, the CSA helps pharmacies allocate and justify resources more effectively, optimize workflows, and the management of the research service.

These areas describe the recent emergence and advancement of research pharmacy. As I reflect on the Summit, I was in awe at the elevation of practice to meet many complexities of research operations, perceiving them rather as new opportunities for improvement and advancement. The atmosphere of dedication, value, and community reflects the purpose behind our daily actions, and contributions these will bring to healthcare. Encompassing these critical functions such as study start-up, maintenance, education, and new clinical services, IDS is positioned at the heart of research operations and drives the success of clinical trials.

References

Abdulsalim, S., Unnikrishnan, M. K., Manu, M. K., Alrasheedy, A. A., Godman, B., & Morisky, D. E. (2018). Structured pharmacist-led intervention programme to improve medication adherence in COPD patients: A randomized controlled study. Research in Social and Administrative Pharmacy, 14(10), 909–914. https://doi.org/10.1016/j.sapharm.2017.10.008

American Society of Health-System Pharmacists. (2018). ASHP guidelines for the management of investigational drug products. Bethesda, MD: ASHP.

Carroll, E. (2024, September 13). Get in the fast lane: An IDS contribution to reducing clinical trial activation timelines [Conference presentation].

Hematology/Oncology Pharmacy Association. (2018). Investigational drug service best practice standards. Hematology/Oncology Pharmacy Association.

McLuckie, R., Song, K., & Yu, M. (2024, September 13). Work hard, report smart: Using the IDS complexity scoring tool to assess effort in clinical trials [Conference presentation].

National Comprehensive Cancer Network. (2022). Investigational drug service consensus recommendations. National Comprehensive Cancer Network.

Park, D., Patel, S., Yum, K., Smith, C. B., Tsao, C.-K., & Kim, S. (2020). Impact of pharmacist-led patient education in an ambulatory cancer center: A pilot quality improvement project. Journal of Pharmacy Practice, 089719002097077. https://doi.org/10.1177/0897190020970770

Sabol, A., & Digiantonio, N. (2024, September 13). Raising the platform: Exploring pharmacy impacts of new trial design [Conference presentation].

Tran, T., Khattar, S., Vu, T. T., Potter, M., Hodding, J., Kuo, G. M., & Le, J. (2017). Impact of pharmacist discharge counseling on hospital readmission and emergency department visit. Journal of Hospital Administration, 6(2), 68. https://doi.org/10.5430/jha.v6n2p68

Yang, W., He, R., Sun, Y., Yan, F., & Wang, F. (2023). Enhancing phase I dose-finding trials design through dynamic borrowing information and handling late-onset toxicity. Frontiers in Pharmacology, 14. https://doi.org/10.3389/fphar.2023.1266322

Zhou, H., Yuan, Y., & Nie, L. (2018). Accuracy, safety, and reliability of novel Phase I trial designs. Clinical Cancer Research, 24(18), 4357–4364. https://doi.org/10.1158/1078-0432.CCR-18-0168

Rachael Aletti, PharmD

Solutions Engineer, McCreadie Group

Rachael joined McCreadie Group in 2019 as an Account Manager, leading new site implementations, optimizing Vestigo at existing sites, and fostering a collaborative community in investigational drug services. She pioneered the growth of the Research Pharmacy Summit and Vestigo’s Customer Success team before transitioning to Business Development Manager, focusing on new contracts and strategic planning. Now a Solutions Engineer, Rachael combines her technical expertise with deep knowledge of research pharmacy management to understand client needs and showcase Vestigo’s capabilities.

With over 13 years of experience as a licensed pharmacist, Rachael has worked primarily in academic medical centers, starting in inpatient care and transitioning to Investigational Drug Services in 2013. She graduated Summa Cum Laude from Massachusetts College of Pharmacy, completed a PGY1 Pharmacy Practice Residency at Montefiore Medical Center, and practiced at Montefiore before joining the IDS at NYP-Weill Cornell Medical Center.