Clinical Researcher—October 2025 (Volume 39, Issue 5)
PRESCRIPTIONS FOR BUSINESS
Michael A. Bishop
Global trials can unlock real advantages for sponsors, including access to diverse patients, faster enrollment, and more representative data across geographies. However, global expansion isn’t always the right move. For every sponsor that benefits, there’s one that overspends, underdelivers, or enters markets they were never built to support. They can get bogged down by operational friction, mismatched protocols, or decisions made too late in the game.
It’s true that going global can accelerate development, but only if it’s done with clear-eyed discipline and the right partners at the table early. In a high-risk industry that punishes missteps and rewards efficiency, the question any sponsor should ask isn’t how to go global. It’s whether they should at all.
What Actually Makes Global Trials Hard
Sponsors sometimes underestimate the complexity of global trial execution, especially in high-need therapeutic areas like oncology, nephrology, and rare diseases.
Global studies are far more complex than single-country studies and tend to fail due to many or all of the following factors:
- Regulatory fragmentation: Ethics board reviews, documentation standards, and startup timelines vary dramatically. There is no “global norm.”
- Operational inconsistency: Every region comes with its own infrastructure, workflows, languages, and cultural norms. If your contract research organization (CRO) partner isn’t fluent in these realities, timelines slip.
- Enrollment ≠ retention: Sponsors often succeed at broad recruitment, only to lose patients midstream due to mismatched care models or burdensome protocols.
- Disjointed vendors: Using multiple CROs, labs, and technology partners without centralized, therapeutic-aligned oversight introduces confusion and risk.
Unfortunately, these are predictable outcomes when global strategy is treated like a checklist rather than as a system.
Determining a Commercial Threshold for Going Global
At late-stage development, especially in oncology or cardio-metabolic disease, sponsors face a critical decision: licensing the asset or pursuing global Phase III trials on their own. That decision hinges on whether the product meets the commercial threshold for global investment.
Determining this threshold involves evaluating a complex array of factors to assess the product’s value, the potential return on investment, and the overall market dynamics. Covered below are some of these factors.
Clinical Development Stage and Regulatory Milestones
- Clinical trial data: The current status of clinical trials (Phase II or Phase III) will heavily influence the commercial threshold. Is the product close to approval, or are there remaining hurdles? Positive clinical trial data in late-stage trials increase the potential value of the product.
- Regulatory pathways: Consideration of any expedited regulatory pathways (e.g., accelerated approval, orphan drug status, breakthrough therapy designation) that could expedite market entry.
- Competing products: Assess the clinical positioning relative to competitors. If there are multiple biologics in the same indication, the differentiation (e.g., efficacy, safety, delivery) will impact the commercial threshold.
Market Size and Potential
- Addressable patient population: This means the size of the patient population and the specific oncology indications the biologic targets. Oncology treatments, for example, often target smaller populations, but with high unmet needs (e.g., rare cancers), which can drive higher prices.
- Current treatment landscape: This concerns one’s understanding of the standard of care and how the new drug fits within or disrupts the existing treatment landscape. For example, is the treatment aiming to improve survival rates, reduce side effects, or offer a first-line treatment option?
- Pricing and reimbursement considerations: Rare disease treatments often face high costs. Key factors here include whether payers are willing to reimburse individuals, potential pricing thresholds based on efficacy, market dynamics, and reimbursement models in different regions (e.g., the United States vs. the European Union).
Competitive Landscape and Market Entry Timing
- Competitor landscape: Determine if there are other drugs in the same space and how your candidate compares. This includes both approved treatments and those in development. Is your drug a first-in-class, or will it be a me-too product?
- Market entry window: Licensing earlier or later in the development cycle could impact the commercial threshold. Late-stage drugs typically offer more confidence regarding clinical efficacy but may face higher licensing costs as the value of the product is better established.
- Exclusive deals or partnerships: Licensing partners often expect a strong competitive advantage. For example, partnering with a company that already has an established oncology portfolio can be a significant advantage in terms of sales channels, marketing, and distribution.
Financial and Deal Structure
- Deal terms: These can vary widely depending on the stage of development. Early-stage deals may offer lower upfront payments with higher milestone payments, whereas late-stage deals will likely command higher upfront payments but lower milestones.
- Risk mitigation: Licensing a treatment at a later stage reduces development risk for the licensee but still requires assessing the commercial risks of competition and reimbursement.
- Commercial potential: This includes a forecast of potential sales and revenue (forecasting market share, pricing models, and market access). Often, this is done using a discounted cash flow model or other valuation methods to project future revenues and profitability.
Manufacturing and Supply Chain
- Manufacturing costs: Complex manufacturing processes can impact both cost and scalability. Assessing the cost-effectiveness of scaling production can be essential in determining commercial viability.
- Supply chain considerations: Some treatments, especially biologics, may require specialized distribution channels. Ensuring the drug can be effectively distributed to clinics or hospitals may influence the threshold.
Intellectual Property and Exclusivity
- Intellectual property: The strength and scope of intellectual property protection around the therapeutic, such as patents on the molecule, manufacturing processes, or delivery systems, play a critical role in determining licensing terms.
- Market exclusivity: Consideration of whether the treatment can maintain exclusivity in the market, whether through patent protection or regulatory exclusivity (e.g., 12 years in the U.S. for biologics under the Biologics Price Competition and Innovation Act).
Partnerships and Strategy Alignment
- Strategic fit: Licensing deals often consider how the treatment aligns with the strategic goals of the licensing company. For instance, does the drug fill a gap in their existing pipeline or open new market opportunities?
- Geographical focus: The geographic territories being targeted (e.g., U.S., European Union, emerging markets) will influence the deal structure. Larger, more profitable markets will likely drive higher commercial thresholds.
Negotiation Leverage
- Bargaining power: The strength of the negotiating parties will affect the deal. The more compelling the data or the greater the unmet need in the specific indication, the stronger the negotiating position of the developer.
- Non-financial factors: Non-financial considerations (such as marketing strength, regulatory experience, distribution networks) may also influence the terms of the deal.
Sensitivity to Failure and Market Risk
- Market acceptance and adoption: Even with promising clinical data, the true commercial success depends on market uptake, which is influenced by physician and patient preference, pricing, and how well the drug is marketed.
- Potential for failure: There may still be regulatory and market risks, such as adverse events post-marketing or delayed approval timelines, that affect the overall value and commercial threshold.
Execution Risk is Where Global Trials Break Down
Once the commercial case is established, it’s time to design the study. However, this is where too many sponsors fall into a familiar trap: they finalize global protocols in isolation without factoring in how trials will actually operate in each geography.
In global trials, a one-size-fits-all protocol rarely works. Standards of care vary. Reimbursement models differ. A treatment pathway that makes sense in the U.S. might be impractical (or even prohibited) elsewhere. Unless sponsors have on-the-ground expertise baked into study design, these disconnects will derail timelines, enrollment, and data quality.
This is one of the most common reasons global trials miss their milestones: the protocol isn’t wrong in theory but it’s unworkable in practice.
Why Experienced CROs Matter
That’s why working with an experienced global CRO, especially one with therapeutic focus, is one of the most overlooked risk mitigation strategies in drug development. When involved early, the right partner can:
- Flag design decisions that won’t translate across regions
- Recommend operational adjustments that improve enrollment without compromising endpoints
- Guide feasibility based on actual site performance and regional standard of care
- Reduce downstream costs, amendments, and delays through up-front alignment
- Work with key opinion leaders active in clinical trials to validate and provide input at regional and country levels
Most CROs don’t do this. They receive a protocol and execute. However, a CRO that understands both development and operations can offer a very different kind of value.
Especially in complex therapeutic areas like oncology, renal, or cardio-metabolic disease, these nuances matter. Trial success is more than just about speed or size. It’s about alignment, and that’s where the best CROs quietly and consistently deliver.
Michael A. Bishop has more than 30 years of business development and life sciences experience with companies including Cardinal Health, PPD, ICON, and, most recently, Ergomed/PrimeVigilance. He has led various CRO commercial teams, including those in business development and global strategic accounts driving business strategy for large pharma and biotech companies.
