Contract medical writers sometimes find themselves hired to write a clinical study report (CSR) (or clinical trial report (CTR)) before their client has prepared all of the information needed for the report. This leads to frustration and causes delays in the CSR development. In turn, delayed CSR completion can extend the actual submission date of the product’s eCTD/marketing application-because CSRs are required content. Thus, the very painful result of delayed CSR preparation is the sponsor’s loss of considerable revenue for every day that the marketing application’s approval is delayed.
Clearly, writing the CSR promptly, at least on study completion, is the wise course of action. Doing this can reduce the cost of generating the CSR, compared with writing the CSR months or even years after the study is closed. And one of the most effective things the sponsor can do to prepare for prompt CSR completion is to have the items listed below available when the medical writer begins drafting the CSR.
The items in this list include some documents and tools that must be available for CSR completion. However, some items are optional. Other items are needed only in specific circumstances, such as when specific clinical trial designs are used. This checklist applies to full-length CSRs that document the execution and completion of clinical studies of drug and biologic investigational products.
All documents listed here should be provided to the medical writer in electronic format, assuming the CSR will eventually be included in an electronic regulatory submission. If the documents are available only as hard copies, they should be scanned for incorporation into the CSR. If the writer only receives hard copies of the documents they need to work with, the cost of the CSR will be much higher than if electronic copies are provided. This is because the writer will have to scan the hard copies to convert them into electronic files in order to incorporate them into the CSR, which is time consuming.
Although PDF-formatted files will be somewhat helpful in drafting the final report, the medical writer really needs the protocol, any amendments, and investigator brochure files to be in Microsoft Word format. This is because the writer must copy and paste into the CSR-specific, verbatim language taken from these documents, especially the protocol. Without a Word file, the writer may have to type the information into the draft CSR, possibly introducing errors and requiring more time to incorporate the protocol text into the report.
When should the writer begin developing a CSR? Ideally, the CSR should be developed in parallel with the clinical study protocol. Although this doesn’t often happen in the real world, the CSR template certainly can be populated with information from the protocol long before study completion and database lock. Then, when the SAS data are available, the rest of the CSR can be completed relatively quickly. This approach saves a great deal of time when compared with waiting until database lock to begin writing the CSR!
The documents that medical writers need to produce a fully ICH-compliant CSR are provided below in two categories, Tools and Administrative Information , and Content:
Tools and Administrative Information
1. Protocol number or study number
2. Study number in ClinicalTrials.gov
3. Number and name of each clinical study site or center
4. Sponsor’s in-house style guide, if applicable, and published style guide, if applicable (eg, AMA Manual of Style, 10th Edition)
5. Clinical study report template in Microsoft Word, if available
6. Adverse event (AE) and/or serious adverse event (SAE) narrative template, if applicable (ie, if there were AEs and/or SAEs reported in the clinical study, and if those events will be written as narratives for inclusion in the CSR)
7. Clinical study report project timeline
8. For interim reports, the cutoff date for clinical study data to be presented in the interim report
9. Name, title, and contact information for sponsor’s representative who will approve and sign CSR; name, title, and contact information for Principal Investigator who will sign the CSR
10. Description of naming conventions for clinical study report files, if applicable
11. Names and contact information of sponsor personnel with whom the writer will work to draft the CSR
12. Information on how to store, archive, and circulate draft and final CSR, if applicable
13. Directions as to who will store, archive, and circulate draft and final CSR
14. Decision from the sponsor as to which investigational product name will be used consistently in the CSR, if applicable (especially if the product name has undergone changes since protocol was written)
15. Names and addresses of CROs used and description of their role in the study, if applicable
16. Sponsor’s content- or process-related SOPs that apply to writing clinical study reports
17. Description of sponsor’s ideal label for the investigational drug product (optional)
18. Clinical development plan (optional)
19. ICH Guideline E3, The Structure and Content of Clinical Study Reports
20. FDA Guidance for Industry: Submission of Abbreviated Reports and Synopses in Support of Marketing Applications, if applicable
21. European Medicines Agency (EMEA) – Note for Guidance on the Inclusion of Appendices to Clinical Study Reports in Marketing Authorisation Applications, if applicable
1. Clinical data as tables, listings, and figures (TLFs)
2. Screening logs for subject disposition (if not provided in TLFs)
3. Case report forms (CRFs) of subjects who had serious adverse events (SAEs)
4. Milestone study period dates: dates when first subject enrolled, last subject enrolled, and last subject completed study
5. List of IRBs/IECs/DMC addresses and chairperson’s name
6. Sample study-specific master Informed Consent Forms for protocol and all amendments
7. Study-specific case report forms (CRFs)
8. Safety (AE and/or SAE) narratives, if applicable
9. Statistical Analysis Plan (SAP; sometimes called the Data Analysis Plan, or DAP), if applicable
10. Pharmacokinetics (PK) report, if applicable
11. Pharmacodynamic report, if applicable
12. Toxicology report, if applicable
13. Immunogenicity report, if applicable
14. List of references (abstracts or manuscripts) from publications derived from clinical study data
15. PDF files of all medical literature supporting the study and cited in the CSR
16. Original clinical study protocol and all amendments (strongly preferred as Microsoft Word files)
17. Investigator brochure (versions used in the study, preferably as Microsoft Word files)
18. Chairperson and address of DMC/Steering Committee, if applicable
19. List of site names, numbers, and locations
20. Name of the company that managed the clinical trial supply
21. Names and addresses of laboratory facilities used
22. Laboratory certificates and normal ranges for all laboratories
23. Investigators’ CVs (as PDFs or scans)
24. List of investigational drug batch numbers and list of subjects (by subject number) receiving each batch of investigational drug (Note: This is often the hardest information to acquire for the CSR.)
25. List of protocol violations and/or deviations (if not included in TLFs)
26. List of investigators and study personnel, mailing and e-mail addresses, telephone and fax numbers ; if lead principal investigator, identify and include contact information
27. List of names and contact information of sponsor’s personnel who participated in the clinical study: medical monitor (usually an MD), biostatistician, and clinical research associate(s)
This list is a reflection of my experience directing medical writing departments and doing medical writing since 1995. The information in this post isn’t intended to be definitive. Each individual clinical study may require documents that I haven’t mentioned here; conversely, some studies won’t require some of the document types that I’ve listed. Consult the relevant regulatory guidelines to verify the kinds of documents required for preparing your ICH-compliant CSR.
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