Once all the subjects have gone home, the samples have been analysed, the data crunched and the results interpreted, the clinical study report (CSR) remains the only narrative detailing the delivery of your study. Memories fade, key personnel move on (or retire) and content of study ‘summaries’ (in documents like the Investigator’s Brochure) are constantly reducing. The CSR is not just a requirement of regulatory reporting but also a critical contributor to collective corporate memory, emphasising the importance of producing timely, accurate and well-written reports (http://www.niche.org.uk/asset/insiderinsight/ Insider-Clinical-Study-Reports.pdf). Quality control (QC) plays a vital role.

As a reviewer, the best time to perform your QC can vary depending on the nature of the project. When done with the right checks and balances, it can take place during the CSR drafting process, which has the advantage of more relaxed timelines, or wait until CSR finalisation, which guarantees that the final product is included in the QC. In any event, a formal QC step is essential under all circumstances, and it should be factored in advance when developing CSR timelines. The QC is much more than just a read-through or a ‘review’, as it must include a 100% check of the information in the CSR against the source information. The QC must be conducted (usually by an experienced medical writer) by someone not involved in writing the CSR. Although the CSR author is thoroughly familiar with the narrative and the source materials, they are susceptible to what writers term ‘word blindness’.

Furnished with the source documents, including the study protocol, statistical analysis plan and data package (tables, figures and listings [TFLs]), most reviewers are often eager to start confirming the study details. However, I prefer to initially perform a more comprehensive review of the CSR, including areas that are frequently overlooked by authors. This includes: ·

• Ensuring that the CSR’s title exactly matches that of the protocol
  • That the document version is stated correctly throughout
  • That the page headers and footers are sized correctly to fit the page orientation and are consistent across the entire document
• These characteristics of the document can indicate a great deal about the care with which a report has been prepared.

Effectively, previewing allows me to focus on the task at hand by ensure consistency of appearance and adherence to an agreed-upon medical writing style guide. An important aspect to check is treatment group nomenclature, ensuring consistency throughout the document; often variations are introduced during study conduct. Descriptions that remain consistent throughout a document suggest a fully reviewed and polished document. Pagination should also be considered, making sure there are no unwanted blank pages or large areas of white space caused by incorrect positioning of page breaks. The ‘Print Preview’ function in Microsoft Word is the best way to review the ‘look’ of the document  before focusing on the text itself. Through this function, the following can be quickly checked:

• Blank pages
• Incorrect gaps between paragraphs
• Tables split across pages
• Incorrect justification

Such previewing may seem minor, but it is a great way to familiarise oneself with the CSR and get a ‘feel’ for the document’s overall structure. Familiarisation will assist with time management and delivery planning.

A formal QC requires a systematic approach involving appropriate checklists directing a step-by-step approach. The QC must follow the appropriate CSR template and style guide as well as the relevant QC standard operating procedures (SOPs)—for performing the QC itself and producing the CSR. It can be helpful to QC check the methods first, to gain a better understanding of the study design before addressing the results. This involves confirming that the information presented reflects the source materials (e.g., protocol and amendments as well as any statistical analysis plans, study reference manuals and/or file notes). The statistical methods in a CSR (contained in Section 9.7 of the CSR as per International Council for Harmonisation E3 guideline; https://www.ich.org/page/efficacy-guidelines) are often sourced from the statistical analysis plan rather than the protocol. The rest of the methods, including the details regarding Ethics and Investigators, the Introduction, Objectives and remaining aspects of the Investigational Plan, are principally sourced from the study protocol.

The principal task with regard to the results is to perform a 100% data QC, that is, verify all cited data against the source data (i.e., TFLs). When checking data against the TFLs, it is essential to confirm meticulously that data appearing in the in-text tables match the source documents. Additionally, I also must ensure that each in-text display, whether it is a table or a figure, contains a footnote featuring the data source; this is usually a table or figure number from within the TFLs. Further, these QC checks must also confirm that all data (i.e., numbers/statistics) in the text of the results also match the source documents. Even if there are no mistakes, it is considered best practice to keep a formal record of the review, leaving a comment stating that the table/statistics appearing in a paragraph have been checked. Data checking can be the most time-consuming task carried out during a QC; however, this investment in time and attention to detail ensures that the aspect of the report most prone to error—transcription of data from TFLs—is correct, thereby guaranteeing high-quality standards in a regulatory document.

Internal consistency of the data presented in the CSR is also essential. After verifying the results sections, the Conclusions are also checked to make sure they accurately reflect what is stated in the main body of the results. Any statements in the Discussion section that pertain to study results must also be checked against the main body of the CSR. Similarly, the synopsis must also be cross-checked against the main body to ensure consistency. The CSR synopsis is often prepared at some unspecified point during document development (often when the writing team believes that the CSR is ‘ready’) and is a section prone to error. However, the body of the CSR may undergo further changes (following client review), and those changes are not always captured in the synopsis. When study conclusions are presented as bullet points, these are usually repeated verbatim in the synopsis, and it is important to check these carefully against the corresponding conclusions in the main body, especially as inconsistencies can often creep in during the various review rounds.

Overall, a CSR should be checked for consistency of presentation, format, grammar and spelling. The type of English spelling followed (United Kingdom vs. United States) should be consistent throughout the document; although authors/reviewers are not always familiar with the punctuation conventions that differ between the two, so I also check for punctuation as well as spelling. When reviewing, I also make sure that the in-text tables and figures follow a consistent presentation style and are in line with the applicable style guide.

In addition, I check that numbering of in-text displays is sequential and in keeping with the CSR template. I am sure to read through the table of contents to ensure sequential numbering of headings and subheadings, as well as the use of capitalisation. It is not uncommon for there to be inconsistencies in the use of ‘Title’ case (all words capitalised) and ‘Sentence’ case (only the first word capitalised) in the various headings, titles and captions in a document. I also ensure to update the table of contents, along with the list of tables and list of figures (if these are included).

Checking the correct and full listing of the abbreviations is also necessary. I ensure that all the terms present in the abbreviations list at the start of the CSR are used consistently in the document, and that all abbreviations used in the document are reflected in the abbreviations list. Abbreviations must be defined on first use in the CSR, and it is advisable for definitions to be provided in the synopsis and also on first use in the main body (the synopsis serves as a standalone document in regulatory submissions). In addition, I also check the formatting of the list of references, as well as ensuring that all publications that feature in the reference list are cited in the document. Hyperlinks in the CSR (i.e., cross-references to in-text displays, document sections and references) are also checked to guarantee they are functional and link to the correct location.

When reviewing, I strive to be thoughtful, clear and precise when providing QC ‘comments’. By citing the relevant place in the text, source table or listing number in the comment, the right source data can be located by the author. I also include ‘global’ comments when necessary (i.e., repeated errors indicative of a training issue) but the QC must highlight all cases of any text-based changes. Any information that cannot be located in the source materials is marked as ‘Unable to verify’ or ‘UTV’. If the QC tasks includes checking the document against writing style requirements (defined in a specific writing guide), I will refer the authors to the relevant section of the guide, thereby helping the authors better understand the error. Similarly, where defined in the QC process, I also include spelling and grammar tips to help the authors avoid mistakes in the future and provide a rationale for changes made to the text—every document is a learning opportunity for both the writer and reviewer.

When finishing up the review, it is good practice to note in the QC review form a statement noting that a 100% QC check has been conducted and cite the source documents used, along with their dates and version numbers. Before returning the document to the authors, I will read through the comments to ensure that they are easy to understand. It can be daunting for authors to receive QC comments, which are often numerous and detailed, so one last check for clarity will ensure the handover and revision of the text goes smoothly.

Comprehensive QC reviews are intensive and require attention to detail, but this process can be aided by conducting the review in an organised manner. Using thorough QC checklists, and the points covered in this article, will help to produce high-quality documents. Caitlin Tolbert is the House Editor and a Senior Medical Writer at Niche Science & Technology Ltd.