MicroEvals

1. BACKGROUND 1.1. Regulatory reader • Busy • Decision Maker • Highly selective 1.1.1. Reading behavior • Surveying  Skimming through text quickly to get a general sense of its content and organization.  Studies have shown that readers often survey text before reading it in detail. This helps them identify relevant information and prioritize their reading.  Surveying involves scanning the document to get a general sense of structure and major topics without deep reading.  Readers use this method to identify relevant sections quickly and determine whether the document warrants closer attention.  Implication for writing: a) Ensure that headings and subheadings are clear and meaningful. b) Use bolded key terms and bullet points to enhance initial scannability. • Distinguishing  Identifying the main ideas, supporting details, and relationships between them.  Research indicates that readers are adept at distinguishing between key points and supporting information. However, this ability can be hindered by poorly structured or complex text.  Involves differentiating between relevant and irrelevant content based on the reader’s immediate needs.  Selective focus is placed on sections that directly address the reader’s regulatory questions or decision criteria.  Implication for writing: a) Use clear topic sentences to set up paragraphs and help readers decide if the content is relevant. b) Position summary points at the start of sections or paragraphs. c) Avoid excessive detail unless it directly supports the regulatory decision.  • Chaining  Connecting new information with prior knowledge and experiences.  Studies have shown that readers actively chain new information with their existing schemas to create a coherent understanding. This process is crucial for effective learning and comprehension.  Chaining involves following a logical sequence of information across sections to understand relationships, such as linking results to conclusions.  Readers use this method to trace arguments and verify the flow of reasoning and evidence.  Implication for writing: a) Ensure logical flow between sections and paragraphs. b) Use transitional phrases to guide the reader through the argument or evidence chain. c) Develop content that connects results to conclusions clearly, aiding the reader in following the chain. • Extracting Satisficing  Selecting and retaining specific pieces of information from the text.  Readers often extract information that is relevant to their goals or interests. However, their ability to extract information accurately can be influenced by factors such as text complexity, volume of data, and data reading comprehension skills.  Extracting involves pulling out specific, critical information (e.g., study results, key data points, conclusions) without reading the surrounding text.  Readers use this method to retrieve precise details needed for decisions.  Implication for writing: a) Present key data points in tables or lists for easy extraction. b) Use concise summaries at the end of sections to aid in extracting main points. c) Ensure that key findings are easily accessible, ideally through bullet points or highlighted results. • Impact of Surveying and Extracting  Likely see only 50% of page  If read, will read less than 35% of the page  1.2. Writer’s Role It is up to the writer to bring perspective, analysis, and interpretation to the data, guiding the reader along the pathway toward shared understanding. It is the writer's responsibility to present the information in a clear, logical, and accessible manner. The objective is to ensure complex ideas are communicated effectively. 1.2.1. Plain language • Plain Language Movement/Initiatives (US/UK/FR/DE; see Table 7 for more knowledge) The goals of the plain language movement are to create documents that help • readers: • Find what they need. • Understand what they find the first time they read it.  Use what they find to accomplish their work. • How benefits regulatory reader:  Improves the ability to locate key information quickly, which aligns with the skimming and selective reading habits of regulatory agents.  Reduces the need for look-back reading as the content is more likely to be understood on the first pass.  Promotes better understanding of complex data, supporting more accurate evaluations. • Implications for writing:  Lead with the main point (the So what?)  Use active voice to support clarity  Break complex information into bulleted lists or tables to support faster scanning and extraction  Avoid unnecessary words, redundant phrases to support clarity 1.2.2. Definition 1.2.3. Mortal sins of medical writing: • Lack of clarity • Irrelevant content • Excessive verbiage 1.2.4. Work Definition • Focus on what the user or reader needs to do at this location in the document • Prioritize essential information by ensuring the most critical elements supporting the “So what?” are presented first • Slash verbiage, eliminate redundancy, eliminate description • Make the text accessible from many directions • Present information visually whenever possible and use easy-to-follow visual design • Tom: put some important data in the text is necessary. -> Greg: no! 1.2.5. Document User Experience (UX) — 5 Elements: This diagram considers the 5 components that impact how easily regulatory readers can use your documents. • Interaction Design: focused on how the reader uses the document to accomplish what task or tasks. Considers how the reader is likely to navigate within and across sections. • Information Design:  is concerned with how clear and understandable  is the messages and concepts presented in the document.  is concerned with organization and presentation of information.  Tailors the level of detail to the target audience, considering what the reader wants to accomplish and their background knowledge.  Information design is essential to the success of all regulatory writing projects. Information design entails more than just the physical appearance of documents, though visual design is important.  Problems of dense technical writing in large scientific documents: 1) Poor Readability: Dense technical writing often uses complex sentence structures loaded with data. 2) Cognitive Overload: Reading dense technical writing requires significant mental effort, which can lead to cognitive overload and fatigue. 3) Reduced Engagement: Dense technical writing is often only skimmed and not read slowly and in full detail. 4) Negative Perception: Dense technical writing can create a negative perception of the document in the mind of the reader. • Written Language: refers to the use of clear, concise, precise, simple, and consistent language.  Clear and concise language: avoiding unnecessary words and phrases, and using simple sentence structures.  Precise language: Using specific language that is uambiguous.to illustrate complex concepts. • Interface Design: TOC layout, intuitive headers, hyperlinking strategy, and responsive typography.  Clear and consistent navigation: Using a well-structured table of contents, clear headings and subheadings, and intuitive hyperlinks to guide readers through the document.  Responsive design: Ensuring that the document tables and figures are optimized for different screen sizes and devices to provide a seamless reading experience. • Graphic Design: Visual communication, table/figure formatting, and strategic use of white space. refers to the visual communication of information through typography, tables, and figures.  Makes the content easier to read and to understand. • Effectively use white space to improve text readability. 1.3. Lean Writing 1.3.1. Goal • The primary goal of lean writing is to ensure most critical information is identifiable and prominently placed. • Lean writing demands brevity, best achieved through page limits. • A useful practice for document development teams is to map out page counts, ensuring all writers work to targeted lengths. • Writing to a targeted length compels writers to be economical, sharpen sentence structures, and ensure every word counts, thereby eliminating unnecessary details. 1.3.2. Definition • Blaise Pascal in Lettres Provinciales (1657), wrote in French: Je n’ai fait cette lettre-ci plus longue que parce que je pas eu le loisir de la faire plus courte. This translates to “I have made this letter longer than usual because I lack the time to make it shorter.” • Everyone seeks to make writing clear, and one sure route to clarity is writing no more words than necessary. • When writing is lean, when it employs the fewest words possible to the greatest effect, communication becomes more efficient and emphatic. • Focused and concise communication style that eliminates unnecessary information, ensuring that only essential, well-structured content is presented. • Prioritizes clarity and efficiency, helping regulatory reviewers quickly understand the key points without wading through extraneous details. • Focused and concise communication style that eliminates unnecessary information, ensuring that only essential, well-structured content is presented. • Prioritizes clarity and efficiency, helping regulatory reviewers quickly understand the key points without wading through extraneous details. 1.3. The primary goal of lean writing The primary goal of lean writing is to ensure most critical information is identifiable and prominently placed. 1.3.3. Techniques To help your reader, emphasize what is important and downplay what is not. Move background and less important information out of the way. Use the following techniques to emphasize information: • Before drafting the document, determine the key messages you want to convey:  main findings  implications  conclusions of your development work • Position key messages at the beginning of sections (Move the most important claims or main messages to the front. Use first position (document or subsections) to feature prominent information), in summary tables, and within highlighted text boxes tied to figures • Repeat key messages judiciously to reinforce their importance at various points in the document (Announce key claims or messages in topic sentences, at the beginning of sections or paragraphs. When useful, end paragraphs or sections with strong clinching sentences) • Format the most important claims or data so they stand out visually. Use below to focus reader attention on the most important information:  Bullet  Italicized statement {不是为了重要内容，为了区分？}  Bolded words {在table里highlight 重点}  Single-sentence paragraphs • Use the summary and concluding sections of a document to focus on important findings, meaningful claims, and new learnings. Provide true discussions and conclusions, not repetitions of results • Build tables and graphs to emphasize the important data and deliver clear messages. Design tables and graphs so the important data points stand out. Remove data that does not support decision making. 我们提供结构化，easy to find的文档，但不去决定哪些是HA reader想看到，哪些是比较少想看到。 • Use the text near a table or graph to comment on and highlight what is most important to understand from the data. • Follow the 5 – 5 – 15 Rule  ≥5 paragraphs per full page of text  ≤5 sentences per paragraph  ≤15 words per sentence • Use hyperlinks:  Hyperlinks can enhance the lean writing approach by connecting readers to supplementary information without overloading the main document. The strategy involves:  Using hyperlinks to direct readers to methodological descriptions, supplementary data, additional studies, or publications that support your interpretations or discussion points.  Ensuring hyperlinks are clearly labeled and placed at relevant points within the text to allow readers to decide whether to follow a link and to facilitate easy access to supporting document.  1.4. Strategic writing 1.4.1. Different regional regulatory framework A notable case study of the PMDA’s drug approval process is the approval of quizartinib, a FLT3-ITD inhibitor used for treating acute myeloid leukemia (AML). This case highlights the differences in regulatory decision-making between the PMDA and other global agencies, like the FDA. While the FDA initially rejected quizartinib due to concerns about its overall survival benefits, the PMDA granted approval, emphasizing the drug’s potential for a specific subgroup of patients who had no other treatment options. This approval decision was partly influenced by Japan's regulatory framework, which allows flexibility in addressing unmet medical needs, especially in cases where there are few therapeutic alternatives. -思考regional相关内容的想法，特别是与全球不同的情况。 -M2.5中加入真实世界研究，也要从支持labeling角度出发。 1.4.2. Any specific considerations from pre-HA communications? (Confirm with RS during storyboard) 1.5. Mission critical concepts: 1.5.1. Positioning 1.5.2. Reasoning 1.5.3. Summarizing 1.5.4. Synthesizing 1.6. Collaborative planning 1.6.1. Storyboarding 1.6.2. Nutshelling 1.7. Words Usage 1.7.1. Better not to use 1.7.1.1. Clinically meaningful efficacy “The E-R analyses support clinically meaningful efficacy across the subpopulations with the Drug E 5.4 mg/kg dose in BC subjects.” FDA doesn’t like “clinically meaningful efficacy”, you should interpret how it was clinical meaningful. 1.7.1.1.1. Definitions for terms {conflict to above contents} While clinically meaningful and clinically significant {do we use clinically significant?} are often used interchangeably, clinically meaningful emphasizes whether a treatment effect is large enough to make a noticeable, real-world difference for a patient, while clinically significant focuses on whether a study finding is relevant to clinical practice and could potentially impact patient care, even if the magnitude of the effect is not necessarily large enough to be perceived by the patient; both terms involve a subjective judgment beyond just statistical significance The term clinically meaningful is used by the FDA to describe a change or effect observed in clinical trials that has a real and significant impact on a patient's health, well-being, or daily functioning. The concept goes beyond mere statistical significance, aiming to reflect changes that are perceptible and valuable from a clinical perspective. How the FDA Views Clinically Meaningful Changes:{是否下面的endpoints才能说明clinically meaningful？？和前面才不矛盾} (当拿到数据，可以下clinically meaningful的时候，和CD等部门了解这个结论的支持) • Patient-Centered Focus: The FDA and EMA emphasize that clinical meaningfulness should be viewed from the perspective of the patient. This means looking at outcomes that genuinely affect how patients feel, function, or survive. For example, a patient-reported outcome (PRO) that captures improvements in daily activities or quality of life would be considered clinically meaningful. • Within-Patient Change: Recent FDA guidance has shifted focus towards within-patient changes rather than just comparing group averages between treatment and placebo arms. This means that the FDA now looks more closely at whether an individual patient's improvement (or lack thereof) crosses a certain threshold that can be deemed clinically meaningful to that patient, not just based on statistical group comparisons (i.e., minimal clinically important differences). • Anchor-Based Methods: The FDA recommends using anchor-based methods to interpret clinically meaningful changes. These methods link the change in clinical outcome assessments (COAs) to external variables that are more intuitively understood or already established as clinically relevant. For example, in trials for Alzheimer’s disease, the focus may be on measuring cognitive improvements in terms of patients' ability to perform daily tasks, rather than solely on cognitive test scores. • Surrogate Endpoints: The FDA sometimes allows the use of surrogate endpoints (e.g., blood pressure reduction as a surrogate for heart disease outcomes), but only when there is a well-validated and clear relationship between the surrogate and a clinically meaningful endpoint. • Medical writers should differentiate between statistical significance and clinical relevance. 1.7.1.2. Generally “Safety data from Study 3 were consistent with the known safety profile of Drug A…generally occurred at comparable rates in the Drug A and placebo arms.” “For the overall study periods, the types and severity of TEAEs were generally similar…” “Generally”: what reader will do next? Why are you not comfortable with your judgment? You should be careful to choose the word because it seems you are not confident. Always be thinking about what are the cores. 1.7.2. Similar vs Comparable vs Consistent （再理解一下） Similar: Making a comparison on a large scale of numerical measurement. Describes when the new drug's effects are akin to those of a known drug. Example Sentence: “The clinical efficacy of the new drug was similar to the standard therapy, as both showed equivalent reduction in tumor size.” Similar: means having characteristics or qualities that resemble or are alike, but not necessarily identical. The comparison is qualitative in nature as the approach lacks use of metrics. Example: The efficacy of Drug A is similar to that of Drug B in treating the condition, although their mechanisms of action differ. Consistent: Indicates that the drug's effects are uniformly observed across different trials or patient groups. Example Sentence: “The safety profile of the drug was consistent across all clinical trials, with a similar incidence of adverse events reported.” Example Sentence: “the observation of TEAE in this study for China vs global with consistent pattern” Consistent: refers to observations made over a time period. Example: TEAEs rates were consistent between all ethnic groups in the study. Comparable: (China vs. Global) Suggests that the data from the new drug can be directly compared to another drug due to similar characteristics or study conditions. Example Sentence: “The trial design ensured that the efficacy and safety data of the new drug were directly comparable to those of the existing medication.” Comparable: refers to two or more things that are capable of being compared because they share measurable features or metrics. Example: The PFS for all patient subgroups are comparable. In summary:  Similar is used when the outcomes are roughly the same.  Consistent is used when the results are uniformly repeated.  Comparable is used when a direct comparison is valid and meaningful.

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