The Power of Protocol in Oncology Drug Development
September 3, 2025Oncology trials are a crucial tool in helping researchers discover how to treat, prevent, and screen for different types of cancer. In these trials, science and strategy must go hand-in-hand. Study protocol plays a critical, though often underestimated, role in the success of clinical trials. A protocol takes the form of a document that ensures regulatory compliance, but it’s so much more than that. It’s the blueprint for the entire clinical trial, one that keeps the trial together by uniting scientific rigor and business sense.
Hali Beeson, Director of Data Informatics at Atlantic Research Group (ARG), believes the most important consideration is the foresight to plan backwards from the ultimate goal: regulatory submission, approval, and clinical impact.
“Writing protocol with an endgame in mind is the best path forward,” Beeson explained. “It allows you to plan more efficiently, which ultimately helps cut costs that can be accrued from re-work or additional studies added to support some aspect of the submission.”
Planning the Protocol: Start with the Endgame
It’s tempting to dive straight into what a scientist or sponsor wants to measure, but in oncology drug development, the endgame drives everything. The primary target is almost always FDA approval (or its EMA counterpart in Europe), so the real question is: What do these regulatory agencies need to see?
The hallmark of strategic protocol development is to work backwards from this goal. Not only does this streamline decision-making and cut unnecessary costs, but it ensures that every step and every data point serves a clear, regulatory-focused purpose.
What Do Regulatory Agencies Require?
For any indication, understanding the requirements is the first step. The FDA website offers an abundance of guidance documents. Some areas, like IgG studies, are highly specific, while others are less prescriptive. In both cases, you need to take the following steps when creating a protocol:
- Review all available guidance for your type of cancer or indication.
- Study the successful pathways that precede yours.
- Consider how each study in your program builds toward the final approval package.
Oncology Trials: The Big Picture
Oncology drug development generally follows a well-trodden path: Dose escalation (Phase 1), expansion (Phase 2), and confirmatory studies (Phase 3). Even in such a structured landscape, every protocol must be tailored to its unique context. This means that while working hard on the study in front of you, you need to consider the steps along the way in order to help consult on the program as a whole. When writing phase 1, Beeson explains that you need to have phase 2 and phase 3 in mind. You need to be thinking three steps ahead at all times.
“Think, ‘If I’m doing this now, where is this taking me?’” Beeson states. “Thinking on a broader scale, where do you want to take this? It can be easy to focus on what’s in front of you without considering the next thing.”
Here is some guidance for what to consider when creating a clinical trial protocol:
- Safety: Regulatory agencies want robust safety data. This includes all possible adverse events and any indication of harm. Show that the clinical benefit outweighs risk.
- Benefit: Oncology often uses “surrogate endpoints” (like tumor shrinkage) to indicate benefit, but these don’t always capture true clinical outcomes such as progression-free survival or overall survival. As one analogy goes, if your foot is hurting and you cut it off, the pain is gone, but the real problem isn’t solved. Regulators want convincing proof that patients are “not only getting better, but personally feeling better.”
- Statistical evidence: Ultimate approval hinges on statistical proof that benefits are real, repeatable, and clinically meaningful, which is challenging in rare populations.
Biostatistics and The Science of Proof
Strong statistical design provides the proof that a new drug’s effects aren’t just a fluke. But oncology and its funding realities pose special challenges:
- Rare diseases mean small sample sizes. This makes statistically significant results harder to achieve.
- Regulatory agencies view data with skepticism. Every claim must stand up to scrutiny.
- Costs mount fast. Every extra subject, test, and data point adds up.
Early dialogue with agencies like the FDA is key. Submitting protocol drafts and refining the statistical plan based on agency input helps avoid costly delays and trial failure due to a lack of robust protocols.
The Human Side of Oncology Trials
Oncology studies often struggle with the ethics of comparator arms. Single-arm studies compared to published data can be harder to interpret and are more prone to bias than randomized, controlled trials. The indication determines what’s acceptable and possible, further emphasizing the need for both strong statistics and clinical insight. Statistics alone aren’t enough. The blend of biostatistics and medical expertise transforms “numbers” into evidence that guides patient care.
Funding Challenges and Stakeholder Considerations
With cuts to funding from agencies like the NIH, attracting private investment is more important than ever. Investors, especially those with personal stakes, want assurance that money is being spent wisely, the study is bulletproof, and the clinical and statistical risks are managed. A strong protocol can build this confidence.
In oncology drug development, plan for your regulatory “endgame” from the start, think several steps ahead, and let real data and medical wisdom drive your decisions. If you plan backward for success, you pave the fastest, safest, and most efficient path forward. ARG is proud to help sponsors and pharmaceutical companies stay compliant and keep trials efficient with its robust biostatistics program.
