Keeping a programme's documents consistent
A programme's protocols, reports, summaries and other documents carry the same data and messages from one to the next, so they have to say the same thing in the same way. That consistency rests on conventions and a lexicon agreed before drafting starts, on choices where authorities' own conventions differ, on master documents that lock what should not change across studies, and on writers who know where each document sits in the product's lifecycle and carry each change through to the documents it reaches.
Programme conventions and the convention style guide
A drug development plan usually provides for several studies, and it is useful for the project team to agree on a common format for their documents within the framework of the regulatory guidelines. Agreement at the outset speeds up the production of documents and assures consistency. Standard text components can be used in several or all of the protocols and study reports.
A convention style guide is a reference document, built as early as possible in a programme, that puts together key messages, some level of storyboarding, the mechanism of action and the nomenclature, so that the team uses the same verbiage across every document from the start; anyone else who needs to know about the molecule uses it too. Built at an early stage, it is a critical reference later, as the compound advances through its lifecycle. In 2024 one nonclinical writer described building one as very common across the pharmaceutical industry, and as very important at the transitions from first-in-human to phase 2 and phase 3, because it keeps the key messages and the content consistent over time. A scientific writer at a small biotech that had no such document made one anyway, so that everyone would be on the same page.
The program lexicon
A program lexicon is a set of conventions that gives program-specific guidance on terminology, so that every author and reviewer writes accurately and consistently within and across documents, from initiation to finalisation. The lead writer creates it with input from every functional area involved.
Consistent terminology helps a reader focus on and understand a document's overall purpose and key messages without distraction, which is especially important in complex studies with many comparisons across treatment and age groups, time points, endpoints, statistical approaches and other variables. Regulators have named a lack of clarity as one of the most frequently identified document-quality issues, and consistent terminology and style conventions within and across documents support clear, high-quality documents. Poor documents may lead to longer reviews, extensive questions from regulators, delays in approval and the possible rejection of a submission, and may affect the review of documents in the same applicant's later submissions. Where documents will be translated, high quality and consistent terminology in the originals are critical for successful translation.
Consistency is hard to achieve. Writers combine sources of differing quality that may use different terms for the same thing, accepted terminology may change over time, and authors, contributors and reviewers from different functions use different terms for the disease, the condition and the study features and for comparing and interpreting the data.
A lexicon names the terms that should be used and should not be used, any exceptions allowed, and examples. It may cover terms for the product, formulation, disease and indication; standard terms for clinical trials; definitions of endpoints, assessments and abbreviations; and cut-offs or rules for interpreting and comparing data. One example lexicon reads:
| Use | Do not use | Notes |
|---|---|---|
| Treatment | Intervention | For example, study treatment and treatment groups. |
| Study | Trial | For example, clinical study. |
| Participant | Subject, patient | For participants in clinical studies; patients may be used for results of real-world evidence or data studies. |
| Comparable | Similar | For results of endpoints with statistical comparisons (P values and/or 95% confidence intervals), usually primary or key secondary efficacy and safety endpoints; results for objectives with hypothesis testing use superior, noninferior or other language as the hypothesis specifies. |
| SARS-CoV-2 infection | COVID-19 infection | For the infection caused by the virus, not the disease. |
| Viral error catastrophe | Viral error induction | For example, drug A inhibits viral replication by inducing viral error catastrophe. |
| Clostridioides difficile | Clostridium difficile | The genus Clostridium is still used for every other species, such as Clostridium perfringens. |
A lexicon can be specific to one document, one submission or one program, or apply to several related programs. For regulatory writers it is an integral part of the focused authoring approach to consistent comparison language, and lexicons are part of the scientific communication platforms that set accurate, consistent language for all communication around a product or disease. Standard operating procedures, overall style guides and standard document templates are invaluable for high-level guidance on authoring, but they are not intended to give specific guidance for documents at the program level. An updated program lexicon available before the first regulatory document of a program is drafted saves time and effort downstream, in authoring, review and team consensus meetings.
A lexicon should be a living document, reviewed and updated regularly as new guidelines and data emerge through the program's lifecycle. Writers often drive its development, implementation and periodic updates, to keep it a living document.
- The writer should meet the project team early in the project to explain the value of a lexicon and, where available, give examples from other programs.
- The writer can then lead the team's discussion of which terms, definitions, rules for interpreting data and exceptions to them go into the first draft; the team can draw the terms from guidelines, clinical conventions, earlier program documents such as the protocol and investigator's brochure, the literature, statistical rules and other sources.
- The draft can be in whatever format suits the team, stored in a central location that cross-functional team members can reach.
- The writer should allow time for discussion, review and cross-functional alignment, and once the first draft is produced, the project team, and anyone it would like to consult, should review it.
- Because different teams may work on different documents, the writer may need to keep reminding new team members of the lexicon's benefits and reinforcing its use before document development starts.
- The writer should seek support from the medical writing program lead or manager when needed to implement the lexicon.
- During quality-control review, it is important to tell the editor that the team authored the document to the program lexicon and to supply the lexicon as one of the sources for the review.
- The team should review and update the lexicon periodically through the program's lifecycle, for example at the start of documents for each new regulatory submission, and the writer should manage the review cycles.
Depending on the clinical landscape in the product's therapeutic area, the lexicon may stay static or change regularly over the program's lifecycle. It can be used for protocols, investigator's brochures, diversity plans, clinical study reports, common technical documents, the product label, response documents, publications, marketing materials and other documents.
Once developed and used, a lexicon can avoid conflict within the authoring team over terminology, data interpretation and presentation, so the team can focus on meaningful results and interpretation at the right level of detail. It can speed up authoring, review and quality control and help meet tight timelines for regulatory responses and submissions. It empowers the writer as document leader to use terminology the team has agreed on, and when different writers develop the documents for submissions made over time, an up-to-date lexicon can help keep them consistent. By standardising terms and definitions it also supports automation, structured authoring and content reuse, and it can be a source file that artificial intelligence tools ingest to produce first drafts of documents that meet regulatory requirements.
Where authorities' conventions differ
Guidance from different authorities on the same kind of document can differ even in its conventions. As one writer of clinical study reports reported in 2007, the ICH and European Medicines Agency guidance on the structure and content of clinical study reports pluralised the abbreviations for institutional ethics committees, institutional review boards and case report forms without apostrophes, as IECs, IRBs and CRFs, while the comparable FDA documents used IEC's, IRB's and CRF's. A government body may take months or years to change the writing style across its publications, so in the interim its departments may be inconsistent with one another.
Master documents and locked templates
Creating content for a programme of clinical trials balances efficiency, programme-level consistency and scientific integrity. Programme-specific document templates are one way to manage such content, but they leave the door open to undesirable edits that increase none of the three. Stylistic edits and changes that do not change the meaning of the template content create confusion for anyone comparing documents across the programme to understand the key differences and their rationale. For example, if four of five studies share a table of contents for a document type and a key stakeholder moves a section in the fifth, or nests it under a different heading, a reader familiar with the other four would waste time searching for the missing section and/or trying to understand why it does not apply. More seriously, changes to the study approach made from personal preference rather than scientific justification can leave data across the programme's studies not easily comparable. A consistent writer working across the programme may serve as gatekeeper and liaise between trial teams to align language and approach as closely as possible, but this decreases efficiency and cannot completely prevent such edits.
The imaging charter shows the master-document approach. FDA guidance that was recent in 2020 defined the imaging charter as "either a single document or a series of technical documents", which made it possible to reorganise its content into two separate documents. An evaluation of a programme-level charter template found that about 80% of its content was expected to stay the same across the programme's studies, and only up to 20% could reasonably be expected to vary with individual study needs and differences. The content was then split into a locked master document holding what should not change across the programme and a trial-specific addendum holding only protocol-specific clarifications and, if applicable, the rationale for any departure from the programme-level approach. The split improved efficiency, and it increased consistency and scientific integrity by discouraging stylistic and unjustified trial-level alterations and separating out the trial-specific information, which also increased transparency. A required and justified programme-level change could also be made once, in the master, rather than in every study document, which removed the potential for additional edits during revision that could have increased variance across the programme.
A split across a locked master and an adaptable trial document may not apply to every type of content, but a modified approach using the same concept can, for example a programme-level template modified to include locked sections. Before applying a master-document approach to a trial document, the question to ask is whether the bulk of its content is specific to a process, system or programme and is not expected to change much at programme level.
Documents across the product lifecycle
A writer can be involved with documents across a product's lifecycle, from preclinical to post-approval, and so has the potential to play an important role in getting data to every stakeholder coherently and seamlessly. Writers have a role in ensuring that the data from one document connect to the next. An important first step is for the writer to understand how the documents fit into the lifecycle. The common technical document, whose structure ICH M4 sets out, is a good place to see how the clinical documents are structured, and the post-approval regulatory requirements of various countries give an idea of the documents that follow approval. Writers are usually exposed to one document at a time, with so much focus on the document itself that the big picture is sometimes not provided or not clear, and a little proactiveness in understanding the overall lifecycle and when each document is required would go a long way towards making the writing itself clearer and more robust. One way for writers to learn each document in the continuum is to look at its templates and at the structure of documents already written, and writers can learn from the teams that work with those templates or find them online. It is important for writers to know and follow the guidelines not just of the document in hand but of the other templates in the continuum, especially as they take on senior roles in the team.
Data from one document usually flow into one or more downstream documents: protocol sections form the shell of the clinical study report, and the report's results go into summaries, investigator's brochures, manuscripts and others. Understanding those connections saves the writer time by making sure each document captures all the necessary data, so that they are available to later documents. This takes efficient collaboration with other departments and other writers to get all the data a document needs. A document with all the necessary data would help downstream writers keep to timelines and help submissions go in on time.
Even though it is sometimes challenging, resources should where possible be forecast and planned ahead so that the same writer is available for most documents of a single study, which ensures better continuity in the flow of data and in writing style from one document to the next. Where that is not possible, especially with outsourced writing, it is especially important that the lead writer ultimately managing the submission package makes sure every document tells the same story, with the results in the clinical study report reflected in the investigator's brochure, the summaries and the manuscript. For consistency across documents, every stakeholder needs to be kept informed of updates and changes, so that the messaging stays uniform across the documents, and writers play a crucial role in this.