Regulatory writing is often misunderstood as simply the ability to craft technically correct, well-structured sentences and to organize content within templates. In reality, great regulatory writers are strategic thinkers, skilled analysts, and expert communicators who bridge science and regulatory expectations.

While strong writing is foundational, what truly sets great regulatory writers apart is their ability to think like regulatory reviewers. Many of you reading this article have heard me say in workshop sessions that “every great writer is always thinking about their reading audience and what their audience needs in documents to facilitate decision-making.” Great regulatory writers bring scientific fluency, regulatory insight, information design skills, and a deep understanding of how health authorities read and decide.

Scientific and Regulatory Fluency
Great regulatory writers do not just write about science—they understand it. Their fluency spans:

• Clinical trial design – Knowing how studies are structured, analyzed, and reported.
• Pharmacology and therapeutic context – Understanding mechanisms of action, PK/PD, and safety considerations.
• Regulatory expectations – Navigating FDA, EMA, PMDA, and ICH guidance with confidence.

While an average writer transcribes and rewords SME input, a great writer interrogates the data, anticipates regulatory questions, and frames key arguments. They engage SMEs with targeted questions, uncover rationales, test assumptions, and shape content into precise, persuasive messaging. Collaboration becomes a strategic dialogue—not just an information handoff.

Strategic Thinking and Persuasion
Regulatory briefing books and Module 2 dossiers are not neutral summaries—they are interpretive and often persuasive instruments. Whether drafting a Clinical Overview or responding to agency queries, great writers shape how the data is understood and weighed. That’s where advanced writing actions come in:

• Justify – Writers explain why a design, method, or decision was sound, drawing on evidence, precedents, and clinical logic. For example, justifying a single-arm trial due to disease rarity or unmet need.
• Argue – Writers build structured cases: making claims, supporting them with data, and addressing counterpoints. Argumentation is central in briefing books, Clinical Overviews, and benefit-risk assessments.
• Interpret – Writers do not just report results—they make the results meaningful. For example, they show what a treatment effect implies contextually in a patient population and how the interpretation supports approval.

Strategic writers weave together data, rationale, and regulatory expectations to guide the reader toward a clear, supportable “So what?” conclusion.

From Data to Knowledge: Mastering the Continuum
Perhaps the most critical competency of great regulatory writers is transforming data into regulatory knowledge—a progression essential to support effective regulatory decision-making:

• Data: Raw clinical and statistical outputs.
• Information: Organized summaries, tables, and figures.
• Knowledge: Interpretation that answers “What does this mean for approval?”

Great writers move beyond reporting to deliver actionable insights. They help regulatory readers see the
implications of the data—and how those implications align with policy, precedent, and public health
goals.

Information Design: Optimizing for Decision-Making
Great regulatory writers are also information designers. They understand how layout, structure, and hierarchy support—or hinder—regulatory decision-making. Good information design lowers cognitive load and accelerates comprehension.

Great writers adapt their approach based on document type, review timelines, and information volume. They help regulatory readers by:

• Placing key insights where readers expect them (that is, top of sections and preceding tables and figures).
• Minimizing redundancy to reduce reader fatigue.
• Using formatting and white space to support navigation and retention.

These writers do not just present data, they design documents to enhance regulatory reader cognition.

Final Thought: Great Writers Think Beyond Writing
The best regulatory writers are not just technical specialists. They are strategic partners who combine
writing with science, persuasion, design, and foresight. They transform information into knowledge—and knowledge into action.

Check out my LinkedIn to see what others are saying about this article: ​https://www.linkedin.com/in/gregorycuppan/

A few weeks ago, during a workshop on lean writing for regulatory submissions, I was hit with this
challenge from a participant:
“Greg, we overload documents with details and redundancies because of the huge FDA Medical
Review Officer (MRO) turnover. We need to make it easy for new people. New reviewer, limited
context—we’ve got to give them the story in one place.”

​He cited some details that I’ve since seen echoed elsewhere:

• FDA medical reviewer turnover in some divisions exceeds 20% annually.
• Average tenure for a medical review officer in certain therapeutic areas is just 2.1 years.
• GAO reports and workforce modernization plans note that high turnover disrupts continuity and institutional knowledge.
• Junior staff are often thrust into senior decision-making roles prematurely.

The concern is reasonable, but the approach is wrong. Here’s the distillation of my response:

High turnover isn’t an argument for long, dense documents—it’s an argument for leaner ones.
Why?

1. Time is short. Overloaded reviewers juggling multiple applications don’t have the bandwidth to wade through bulky documents and ambiguous prose.
2. Verbosity creates risk. Inconsistent repetition and vague writing increase the odds of misinterpretation—especially if submission work is handed off midstream.
3. Volume of information is rising. Larger, more complex studies with more endpoints. Therefore submission loads are up. You cannot mint more hours in a day, you can only take more days to review what has been submitted.
4. RFIs are increasing due to complexity. Unclear writing that is ambiguous, redundant, and provides few answers likely leads to more clarification requests and back-and-forth exchange with FDA regulatory agents.
5. NLP tools are here. For instance, FDA rolled out Project Sentinel in 2017 for triaging safety information. NLP is being explored to automate the review of clinical trial protocols and extract key elements and also in analysis of real world evidence. This means lean writing applying clarity, cohesion, and consistent structure are not just helpful; they’re increasingly necessary.

Still, I wanted to sharpen the counterargument—so I asked my consulting partner Stephen Bernhardt to
weigh in with his thoughts:

Steve commented,
The upside is your workshop participant is thinking about the reviewer’s situation—and that’s good. But
let’s flip the logic.
If I’m new to a review, I don’t want more content. I want better content. What does “better” look like? I
suggest the following:

• Well-designed IBs and Briefing Books with up-to-date information and clear links to key learnings
• Background sections that offer context, not an exhaustive history.
• Section previews and topic sentences that help me quickly scan and sort what I need to read.
• Clear visual design not just for tables and figures, but for text as well. Smart information design is needed to make processing easier.
• Frontloaded main messages in all sections and clear implications that address the “So what?”Navigation cues explaining why I might want to follow a hyperlink and consult another document.

What do new reviewers actually need? The same thing everyone else needs: Documents designed for
rapid comprehension.

And here’s a question I often asked development teams when consulting:
“When you’ve been new to a project, what helped you get up to speed? What slowed you down?”
I cannot recall anybody telling me: “Longer documents would’ve helped.”

Greg (closing thought):
I understand how people worry that lean writing leaves out what they believe is essential context. We
are dealing with conditioned behavior built up in people who are used to seeing obese documents. But
the real risk is this: bloated documents make it harder for new reviewers to find what they are looking
for, understand the “So what?” and then take action—that is, make a decision.
Steve (closing thought):
Let's trust our instincts that tell us that often less is more and that busy readers will thanks us for
documents that are designed to help them make good decisions.

What do you think?
Have you faced similar pushback when advocating for lean regulatory writing? How do you respond to
the “but reviewers need everything in this document, we gotta be transparent, we gotta make it easy
for them by putting everything in one place” argument? Please share your thoughts.

also published on LinkedIn March 16, 2025

The recently published ICH E6 (R3) Good Clinical Practice guidance is set to bring significant changes to the development of clinical trial protocols. The European Medicines Agency (EMA) has adopted E6(R3) Principles and Annex 1 to take effect on July 23, 2025. Other ICH member nations and regions are still in the process of considering E6(R3) implementation. Additionally, Annex 2, which provides guidance on pragmatic and decentralized clinical trials as well as trials incorporating real-world data, is expected to be finalized by ICH later this year.

As the biopharmaceutical industry continues to evolve toward more complex and adaptive study designs, clinical development teams and protocol writers must align expectations and approaches with these new regulatory expectations. Understanding the key updates in ICH E6 (R3) and their practical implications in enhancing protocol clarity, compliance, and efficiency is essential for those involved in protocol development.

Key Changes in ICH E6 (R3)
The primary goal of ICH E6 (R3) is to modernize GCP guidance by emphasizing quality by design, risk-based approaches, and data integrity. The guidance states the following:

• The scientific objectives of any trial should be clear and explicitly stated in the protocol.
• The clinical trial protocol as well as the plans or documents for the protocol execution (that is, statistical analysis plan, and monitoring plan, should be clear, concise, and operationally feasible.

Some of the major (R3) updates that impact protocol development include:

1. Quality by Design (QbD) Principles – Protocols must integrate risk-based thinking from the outset. This means sponsors will have to proactively identify and mitigate risks throughout the trial lifecycle—from design to conduct and to reporting.
2. Greater Emphasis on Risk-Based Monitoring – ICH E6 (R3) stipulates protocols should clearly define critical-to-quality factors that influence study reliability and patient safety. Regulatory experts stress that ICH E6 (R3) reinforces risk-based quality management as a core requirement, urging sponsors and CROs to adopt proactive risk identification in study design and monitoring.
3. Clarification of Roles and Responsibilities – This section was added to provide clearer expectations for all clinical stakeholders involved in a clinical research project.
4. Increased Focus on Data Integrity and Transparency – Protocols must outline data collection, handling, transfer, analysis, and security measures in a way that ensures reliability and reproducibility. The guidance also mentions that the information collected on each study participant is scaled to address the trial objectives.
5. Flexibility in Study Design – The revision recognizes the growing use of decentralized clinical trials (DCTs), adaptive trial designs, tele-health, remote data collection, and real-world evidence approaches.
6. Patient-Centric Considerations – There is an increased focus on patient involvement in study design to enhance protocol feasibility and recruitment, and reduce participant burden.

To align with these changes, protocol writers must consider the following concepts:
Structuring Protocols with a Risk-Based Mindset

1. Clearly define how study objectives link to study purpose and prioritize critical-to-quality factors. This concept is all about rationale. In essence, put into writing that is clear and concise how the study will answer the research question.
2. Minimize unnecessary complexity by focusing on essential study parameters.
3. Integrate risk mitigation strategies directly into protocol sections. This concept will require concise and precise language.

Enhancing Clarity in Monitoring and Data Collection Plans

1. Define data collection processes in the protocol with an emphasis on data quality and integrity. This principle now requires more than just saying what we are doing. There is a need to offer rationale of why this plan.
2. Specify risk-based monitoring approaches tailored to the study design.
3. Ensure consistency between protocol procedures and study oversight plans.

Addressing Decentralized and Adaptive Study Considerations

1. Incorporate clear guidelines for remote data collection and telemedicine visits. Hereto, we are talking about ensuring the representation of concepts are clear and written with precise language.
2. Ensure flexibility in study designs is clearly documented and will maintain regulatory compliance.
3. Detail the conditions under which protocol modifications may be implemented without compromising scientific rigor.

Strengthening Patient-Centered Language and Accessibility

1. Use plain language principles where possible to enhance protocol readability for all stakeholders. This concept is grounded in all the principles of lean writing.
2. Clearly describe participant responsibilities, visit schedules, and expected study burdens.
3. Incorporate input from patient advocacy groups where it is feasible to improve study design.

Conclusion
ICH E6(R3) ultimately aims to improve trial efficiency, participant experience, and data reliability. Protocol writers will play a critical role by translating these updated regulatory expectations into clear, actionable, and compliant documents.

also published to LinkedIn March 29, 2025

Regulatory documents are not just technical records—they are tools for decision-making. But too often, these documents are burdened with unnecessary details, redundant explanations, and background that buries the point. Lean writing clears that clutter.

In regulatory writing, every word should do work.
Lean writing prioritizes clarity, brevity, and logic. This approach to writing strips away “filler,” flattens convoluted phrasing, and sharpens the path from “So what?” to the answer and then to the supporting details. Lean writing improves comprehension, speeds review, and supports more confident decisions across protocols, study reports, briefing books, and submission summaries.

Where Does Noise Come From?
Noise creeps in through:

• Over-explaining background and methods that are already in the domain of common understanding.
• Repeating table values in text without adding insight.
• Burying conclusions under layers of “blah, blah, blah” that is used to demonstrate “how hard we worked.”
• Writing in passive voice and using vague generalities or ambiguous qualifiers.
• Using long, complex sentences that test working memory of the reader.

The result? A longer document that unfortunately communicates less.

Why Noise Hurts: Cognitive Load in Regulatory Review
Noise increases cognitive load, the mental effort required to process information. Regulatory readers often need to make high-stakes decisions within very short time periods. When documents are packed with extraneous detail, the regulatory reader is routinely forced to:

• Re-read sub-sections to extract key points
• Skim and scan in an attempt to find what really matters
• Struggle to locate data linked to sponsor conclusions
• Navigate irrelevant “blah, blah, blah” before reaching key concept

These obstacles drain attention and slow review. In contrast, lean writing is intended to reduce cognitive friction. The lean writing style respects the reader’s mental bandwidth with the goal to accelerate reader insight. The ability to get to the "So what?"

How Lean Writing Helps
Lean writing addresses cognitive load by making the structure of meaning visible. Regulatory readers need to quickly see what matters: design rationale, data integrity, safety profile, benefit-risk conclusions. When writing gets in the way of that mission, efficiency—and sometimes trust—suffers.
Examples of lean writing strategies:

• Lead with the “So What?” Start each sub-section with the key point
• Use active voice: “The study demonstrated…” not “It was shown that…”
• Minimize redundancy: Do not repeat tabled data—interpret it
• Keep sentences short: Aim for 15 words or fewer on average
• Use formatting wisely: Bullet lists and tables aid navigation—when used with purpose

Before and After—A Lean Writing Example from My Book: Writing for the Biopharmaceutical Regulatory Reader
Before:
“It should be noted that the trial, which was conducted at 20 sites across multiple regions, was designed in a manner that would enable the evaluation of both the safety and the efficacy of the investigational product in a population that was considered to be representative of the target treatment group.”
After:
“The trial was designed to evaluate safety and efficacy in a representative population across 20 sites.”
Lean writing makes the message clear and reading fast and actionable.

Writing Is a Regulatory Efficiency Tool
Streamlining your writing improves not only readability, but also document quality. Lean writing sharpens the argument, exposes gaps earlier to the authoring team, and helps regulatory readers stay focused on what matters most. In short: lean writing supports regulatory success. Here, I define success as a marked reduction in RFIs and protracted effort to give the regulatory reader the “So what?”

Want to go deeper?
My book, Writing for the Biopharmaceutical Regulatory Reader, shares practical strategies to improve clarity, logic, and usability in regulatory documents. Get the book here https://www.mcculleycuppan.com/books.html

​Want to improve your team’s writing?
I help biopharma teams improve the communication quality of their protocols, briefing books, clinical summaries, and study reports to improve clarity and enhance the regulatory review process. Message me if you’d like to talk about training or document development support.

Been a bit since I’ve posted an article here on LinkedIn. My wheels are still turning on thoughts about writing in the biopharmaceutical space. Perhaps the wheels are turning just a little slower. But, at least the wheels still turn!!

Purpose of this article is to share some thoughts on writing actions that should happen within biopharmaceutical research reports and keystone regulatory submission documents. These are the actions that enable a document to be considered a high-quality communication platform. For each action, I present the associated parameter that describes the action.

Please take 5 minutes to read through this list and if you have further time, please share your comments on the merits of what I have compiled as descriptors of writing actions.

Analyze

• Take apart some complex factor/phenomenon to understand the important elements, identify dependencies, establish trends, or make predictions.

Argue

• Take a position or make a claim and support it with data, evidence, and logical reasoning.

Assess

• Form a judgment based on evidence as to whether an interpretation or action is logically justified.

Compare

• Discuss two or more elements of information to assess the degree of agreement or disagreement in their design, execution, or results.

Be concise

• Communicate efficiently, avoiding unnecessary repetition, wordiness, or ambiguity.

Critically analyze

• Discuss strengths and weaknesses of current understanding, taking positions on the reliability, strength, limitations, and quality of the supporting data. A critical analysis might systematically assess an explanation, theory, argument, data set, study, or comprehensive set of studies.

Describe

• Identify key features, qualities, actions, and decision-making so a reader has a good understanding of what was done and why.

Discuss

• Argue for what is most important or relevant to the case at hand, highlighting strengths and weaknesses, addressing counter arguments, or presenting alternative interpretations.

Evaluate

• Assess the quality of data based on adequate study design, study execution, robustness or consistency of findings, reliability, usefulness, significance, or relevance to real world application.

Integrate

• Compare results from two or more research studies to discuss common or divergent patterns in the data.

Interpret

• Form a position on how to understand research results based on statistical and logical analysis.

Narrate

• Comment on important understandings regarding conduct of research and output of research. Narration might focus on critical data points, specific cases, outliers, expected or unexpected findings, or unexplained results.

Overview

• Provide a high-level introduction to document content at the section and subsection to help a reader orient to the most important understandings. Overviews establish purpose, scope, and sequence for a section or subsection.

Rationalize

• State the logic motivating interpretations, decisions, or actions.

Summarize

• Present findings in a discrete manner with a focus main points, key arguments, and significant data.

Synthesize

• Pull together information from various sources to integrate into a comprehensive whole. Draw connections between ideas, and communicate complex information in a clear and coherent manner to build a logical argument or to establish a new conceptual understanding.