Zen And The Art Of Comparator Supply Maintenance

By John O’Brien

Part 1 of a 3-part series: “Beyond Bulk — Rethinking Comparator Supply for Modern Clinical Trials”

In 2012 and 2013, researchers at the Tufts Center for the Study of Drug Development conducted a comprehensive study of comparator drug use in clinical trials. Their findings were striking: fewer than 40% of clinical trials did not include a comparator or co-therapy, comparator supply consumed up to half of the clinical supply budget for some sponsors, and the industry was spending an estimated $1.5 billion to $2 billion annually on comparator procurement alone.¹ To date, this study has not been refreshed or built on, but we are going to change this starting with this article.

Over a decade later, the landscape that drove those numbers has only intensified. Oncology now represents 41% of all clinical trials globally, with over 2,100 trial starts in 2024 alone.² Trial designs have grown more complex — adaptive platforms, multi-arm comparisons, non-inferiority studies requiring multiple comparator strengths and formulations. Yet when I search for published literature on comparator supply strategy, I find remarkably little advancement. The most substantial recent contribution — the Coppola, Bilgin, and Pannatier article from this magazine’s July 2025 edition— outlines four centralized sourcing models that arrive at many of the same foundational observations that were being discussed a decade ago.³

This is a conversation that has not kept pace with how critical comparators have become. Part of the reason is a lack of dedicated academic and practitioner attention. But I believe there is a deeper issue: the industry has treated comparator procurement as a fixed constraint — something that must be bought in bulk, labeled, warehoused, and pushed to sites months before a patient ever enrolls — rather than questioning whether that assumption itself might be the problem.

I came to this realization through my own experience. As a clinical supply chain manager at a midsize global biopharma focused on oncology, I had comparator orders rescinded when a competitor discovered the purchase was for clinical trial use. I was quoted 150 to 200 percent markups over commercial price when approaching competitors directly. I watched expensive oncology comparators expire unused on shelves — warehoused for months and destroyed because patient enrollment fell far behind planned projections from the clinical team.

These were symptoms of a systemic problem I could not find adequately addressed in the literature. So, in 2022, I set out to study it myself through a master’s capstone project — field research across sourcing vendors, stakeholder interviews with site physicians and supply chain leaders, a legal analysis of insurance cost-sharing, and design of a pilot program. What I found confirmed my suspicion: comparator sourcing is one of the most underappreciated risks in clinical trial operations. This article, the first in a three-part series, explains why.

Why Comparator Sourcing Is Uniquely Difficult

Comparator supply is not just another procurement task. The conventional approach — procure in bulk, push to sites, hope the forecast holds — exposes sponsors to a cascade of compounding risks that, together, create a problem unlike anything else in the clinical supply chain.

The most immediate challenge is time. Traditional sourcing can take anywhere from nine to 15 months from procurement through clinical labeling, GMP warehousing, and site distribution, particularly for expensive targeted oncology therapies or biologics.⁴ Buying earlier in advance may seem like the obvious solution, but instead it yields the opposing problem – comparator products purchased months in advance may expire before patients are enrolled. Eighty-five percent of all clinical trials experience some form of delay, and a single day of delay can cost a company between $37,000 and $8 million in lost revenue.⁵ Industry estimates suggest 30% to 55% of all comparators sourced per trial may expire before use, effectively increasing per-trial budget needs by roughly 50%.^1,6

I have felt this tension personally. During my capstone research, I analyzed a scenario where a sponsor purchases comparator centrally from a lower-cost European market. Even with a lower unit price, the effective cost is driven not just by acquisition price but by how much product must be procured to ensure uninterrupted dosing. After adding 30% overage and replacing roughly 20% of inventory lost to expiry during enrollment delays, the annual cost for a single comparator balloons from $3.9 million to over $6 million.⁷ Local site procurement at U.S. prices may solve for the wastage/expiry issue; however, due to the customary 30% site markup per unit dispensed, the cost would exceed $7.6 million in this instance.⁷

These cost pressures compound with regulatory fragmentation — different brand names, marketing authorization holders, and formulations across countries, plus import/export restrictions and country-specific labeling requirements that make global sourcing from a single market difficult.^4,8 And underneath all of this sits the fundamental demand uncertainty of clinical trials.

I learned this lesson early in my career while managing supply for a pediatric hepatitis C trial. The investigational product had been so effective in adults that it had largely eliminated the commercial need for ribavirin, a comparator we still required for the pediatric study. When I approached the manufacturer to purchase enough ribavirin to finish dosing, they told me the quantity I needed exceeded their entire remaining commercial demand — they would have to produce a custom batch, and it would take over three months. That three months became four, then six, then seven, and then nine as our order was repeatedly deprioritized and pushed out. Eventually, with clinical sites running dangerously low on ribavirin inventory, I abandoned the manufacturer order entirely and pieced together contingency supply from smaller available market batches — each with different lot numbers and expiry dates. Each lot required separate clinical labeling and release, increased depot handling complexity, and introduced additional tracking and reconciliation burden at the site level, driving up our operational costs significantly. The manufacturer then contacted our sourcing vendor, upset that we had not taken delivery of the custom batch — which arrived more than nine months past the original requested date, long after we had solved the problem ourselves. That experience crystallized something for me: in comparator supply, you are never the priority.

Together, these challenges are not just execution failures — they are consequences of an implicit assumption baked into most clinical trials: that comparator supply must be procured in advance and pushed through the supply chain before patient demand materializes. In practice, this means comparator volumes are forecast at or before protocol finalization based on projected enrollment curves, country activation timelines, and assumed screen failure rates, then procured with fixed overage buffers and distributed to depots and sites via IRT-driven resupply triggers. When any of those inputs shift (delayed site activation, slower enrollment, protocol amendments), inventory already in the system cannot adjust in real time, and the result is excess stock aging toward expiry in parallel with localized shortages.

Why Nobody Owns This Problem

Comparator supply touches procurement, clinical operations, regulatory, QA, and finance, but no single function owns it end-to-end. In many organizations, comparator requirements are defined during protocol development without a parallel feasibility or sourcing assessment, then handed to supply chain only after key design assumptions (countries, dosing, enrollment timelines) are already fixed. Clinical teams remain focused on the IMP, while supply chain handles comparator reactively, often after protocols are finalized. The result is a fragmented process where comparator is everyone’s afterthought and no one’s primary responsibility.

The broader literature confirms this. The Coppola article notes that comparator supply decisions are “often made too late.”³ A 2010 analysis described a pervasive “find it yesterday” culture around comparator procurement, where transactional urgency overshadows strategic planning.⁹

My own trajectory illustrates the fragility of progress. After completing my capstone, I designed a pilot to test an alternative sourcing model across two active studies. It was approved — budget, vendor, and studies lined up. Then a leadership exodus derailed execution before launch. Years later, the organization is still trying to restart, re-interviewing the same stakeholders my research had already engaged. When comparator sourcing depends on individual champions rather than embedded process, the momentum leaves when the champion does.

The Known Models — And Their Shared Blind Spot

The Coppola framework offers four centralized models: CMO-led, CRO-led, regional vendor, and in-house.³ The ISPE Good Practice Guide and other industry sources similarly distinguish between transactional and strategic sourcing approaches.^4,9 These are useful frameworks, but they share a fundamental assumption: comparator supply operates as a “push” model. The sponsor procures in bulk, ships through clinical supply chains and distributes to sites in advance of patient need. The differences between the models are about who performs each step — not whether the procurement mechanism itself could be different.

For most of the world, the push model is the only viable option given regulatory constraints. But in the United States, a different set of conditions exists: commercial pharmacy infrastructure, specialty pharmacy networks, PBM-negotiated pricing, and a legal framework under ACA Section 2709 that requires insurers to cover routine care costs for clinical trial participants.^10,11 These conditions enable a fundamentally different approach — one I will introduce in the next article in this series.

What Supply Teams Can Do Now

You do not need to wait for a new sourcing model to improve your comparator supply. Based on both field research and operational experience, there are several practical steps teams can take immediately:  

Get to the table earlier. Push for supply chain involvement at the protocol design stage, not after it is finalized. Earlier engagement allows teams to assess sourcing feasibility, evaluate alternative markets or formulations, and align on realistic lead times before assumptions are embedded in the protocol.  A few additional months of lead time shifts your team from transactional to strategic sourcing and opens options that vanish at the last minute.^4,9

Assign a named comparator owner. Identify one person, per trial, accountable for comparator strategy and supply continuity. Make it explicit in the project charter.

Quantify your actual wastage. Most organizations do not systematically track comparator expiry and destruction. Start measuring it. Your organization’s actual number — not the industry estimate of 30% to 55%— is what justifies investment in improvement.

Challenge the default sourcing approach. If central EU sourcing is the reflex for every trial, run the total cost comparison against alternatives — including the overages, expiry replacement, importation, labeling, and warehousing that central sourcing requires.

Publish what you learn. This field cannot advance on vendor marketing material alone. If your team runs a cost comparison, tests a new vendor model, or even tracks wastage for the first time, share it.¹

Looking Ahead

Comparator sourcing is not an unsolvable problem. It is an under-invested one. In the next article, I will introduce a prescription-based “pull” model for U.S. comparator supply that can cut lead-times by 75%, reduce waste to under 5%, and open cost levers that traditional push models cannot access, for the right comparator. In the third article, I will examine the strategic advantages that model enables — and the legal barriers around government-insured patients that have become harder, not easier, since my 2022 research.

Ken Getz, Terry Walsh, and Mary Jo Lamberti gave us the most forward-looking analysis of comparator sourcing trends when they published their CSDD findings over a decade ago.¹ With oncology comprising 41% of all clinical development and the industry spending billions annually on comparator supply, it is past time for that data to be refreshed — and for a more serious, evidence-based conversation about how to manage what may be the most expensive afterthought in clinical trial operations.

References:

1. Lamberti MJ, Getz K, Walsh T. Tracking trial cost drivers: the impact of comparator drugs and co-therapies. Pharm Exec. 2013;May:34-37.
2. IQVIA Institute. Global Oncology Trends 2025. Published May 2025.
3. Coppola G, Bilgin P, Pannatier S. 4 centralized comparator sourcing models to fortify supply chains. Clinical Supply Leader. July 15, 2025.
4. International Society for Pharmaceutical Engineering. ISPE Good Practice Guide: Comparator Management. ISPE; 2012.
5. Shanley A. Necessity drives just-in-time approaches to clinical trials supply. Pharm Technol. 2021;45(3):58-62.
6. Chen Y, Meinert J, Guo Y. Positioning inventory in clinical trial supply chains. Prod Oper Manag. 2015;24(6):991-1011.
7. O’Brien J. Improving the Comparator Sourcing Paradigm in Clinical Trials. Master’s Capstone/CCP. Brown University; 2022.
8. Dutta T. Strategic comparator sourcing. Appl Clin Trials. 2009;18(4):40-46.
9. Ware M. Transactional vs. strategic sourcing. Appl Clin Trials. 2010;Sep:38-44.
10. Kehl KL, Fullmer CP, Fu S, et al. Insurance clearance for early-phase oncology clinical trials following the Affordable Care Act. Clin Cancer Res. 2017;23(15):4155-4162.
11. Tsui M, Rehal S, Jairath V, Kahan BC. Most noninferiority trials were not designed to preserve active comparator treatment effects. J Clin Epidemiol. 2019;110:82-89.

About The Author:

John O’Brien is a clinical supply chain professional with experience managing comparator sourcing and distribution for global oncology clinical trials. His 2022 master’s capstone (CCP)project focused on re-engineering comparator supply through commercial pharmacy network integration and insurance cost-sharing, including collaboration with researchers at the Tufts Center for the Study of Drug Development, BeiGene (now BeOne Medicines), Myonex, TrialCard (now Veralis), and SupplyRx. This is the first article in a three-part series for Clinical Supply Leader.

Special Mention to Toni-Joy Burke for domain-level review and editing, and all of my mentors who helped me shape and develop this comparator sourcing research: Scott Bailey, Shawn Fletcher, Brian Horan, Michelle Novak, and Ken Getz.