The timely review of your GLP preclinical final report is very important. However, timelines are generally tight, and yours is not the only study that a reviewer* might be working on. So, how do you make the report detailed, yet easy to read?
Based on decades of collective experience conducting preclinical studies and writing preclinical final reports (both GLP and Non-GLP), our team of subject matter experts has outlined what makes a good preclinical study final report.
* Note: The term “reviewer” in the context of this article refers to any individual reviewing the results of a preclinical study to include investors/due diligence teams for funding, grant agencies, regulatory bodies, preclinical consultants, study directors etc.
- Write a detailed executive summary. We can’t stress the importance of this section. Discuss the background of the test article and why the study was conducted, summarize the objectives, methods, results and conclusion in paragraph format. This helps the reviewer (regulatory body or otherwise) get a lay of the land and focus on important data.
- Ensure that these sections are included in the report (depending on who is reviewing the report).
- Personnel – This describes all individuals involved in the study from the study director to the husbandry technician. Be sure to include all credentials. An important part of 21-CFR part 58) is the use of “qualified personnel in the study.” Having credentials helps reviewers know that the individuals with the appropriate expertise performed the study.
- Objectives – List all specific objectives from the protocol. Do not summarize. For example: “The objective of this study was to evaluate the safety of the test article. Safety was determined using the following criteria: absence of adverse events, 5% or less mortality, absence of thrombi.”
- Enrollment Table – Include a table describing the number of animals, animal identification, implant and explant dates, any follow up dates, early mortalities and scheduled termination. Overall duration on study for each animal should be considered for chronic studies.
- Test article description – Describe the test article – your device or product – even though you also describe it in the protocol. Pictures are helpful, too.
- Test article use and disposition – A table here is handy. List lot numbers, manufacturing dates, implant dates and specific animal numbers.
- Test article characterization – The CFR requires that the test article characterization be established. For devices, this means everything from sterility certificates, build records, lot travelers, expiration/stability data etc. Be sure to reference where this data can be found, and attach it in the appendix.
- Animal source and history – Healthy animals from approved vendors are a requirement of a good preclinical study. List the USDA approved vendor’s phone number, name and address. List whether or not the animals have a history of prior use and their condition at the time of the study.
- Methods – This is another important section. The methods generally describe how everything in the study was conducted. This includes procedural steps and frequency for implant, followup and explant procedures, physical exams, body weights, clinical pathology, histopathology, gross pathology, daily observations, or any other procedure or analysis that was performed during the study. Any discrepancies from what the protocol laid out and what was performed should be detailed in logged deviations and referenced in the text accordingly.
- Results – The highest focus! This section should contain all the results from the study, good and bad. Any unanticipated event or finding has to be explained whether it was related to the intended use of the test article.Tables and pictures come in handy in this section.While it is important to attach appendices of pertinent data or contributing scientist reports, it is important to summarize all raw data in a meaningful way within the body of the main report. This ensures the reviewer doesn’t have to “go fishing” in the appendices. Failure to include a raw data summary within the body of the main report will frustrate the reviewer, require additional time spent “searching,” and delay the process. For example: If you have attached a contributing scientist’s histopathology report, ensure you have at least included a summary of those results and some representative pictures in the main body of the report as opposed to “see appendix C.” This is a top area of frustration for reviewers!When describing amendments and deviations, it is important to focus on why, how and if they impacted the quality and integrity of the data and/or the animals’ health and wellbeing or study outcomes. It is important to provide this analysis and describe it in the body of the report in addition to the copies of the amendments and deviations.
- Discussion and conclusions – The discussion and conclusions section of a GLP preclinical report are of equal significance as the results section. Occasionally, study results are not straightforward. That does not mean that the study was not successful. The discussion describes what influenced or influences results and helps the reviewer understand confounding results. It’s unrealistic to expect the reviewer to make their own conclusions. We’ve read reports with one line conclusions stating “The study was successful. No deaths” This is not helpful nor funny in a review situation. The conclusions need to state very clearly whether or not the specific objectives of the study were accomplished. For example: if one objective is absence of adverse events, then, state that based on the results no adverse events were observed. If you have 10 objectives, ensure that every one is stated as fulfilled or not fulfilled in COMPLETE SENTENCE FORMAT. INCLUDE the conclusions from contributing scientists’ reports.When there is a critical, overarching objective like safety, ensure that is also detailed. For example, “this device was found to be safe in the porcine model.” Do not state “See results” in this section. Sometimes conclusions are not straightforward. That is ok. State the facts. Do not exclude data. Never try to make data fit the objectives.
- Label your figures! Nothing is more frustrating than looking at a picture in the final report without knowing what the picture describes. Ensure that the picture is of a good resolution, clear and accurately illustrates the result. It’s not necessary to include every single photo from a study, but any good report should at least have representative pictures.
- Tables are useful, but just make sure your entire report is not one giant table. Complicated tables are difficult for almost anyone to understand. Do not expect the reviewer to automatically understand what the table attempts to share. Preface your table with a description of what the data represents. Also summarize the tabulated data in complete sentence format.
- Attach your appendices. They must be signed, or, if raw data, must be verified. They include:
- Protocol – a must!
- Contributing scientist reports such as, clinical pathology, histopathology, gross pathology and raw data including medication tables, soap tables, weight and TPR tables. Where applicable copies of case report forms, images, test article characterization data to include: stability, sterility and lot history.
If you are evaluating a medical product’s readiness for preclinical testing including GLP testing, or if a previous study has raised questions from a regulatory body, get in touch with our team of preclinical experts via the form below.