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To do this effectively, it is essential that the submission teams have a clear and well developed TPP from the start of a clinical development programme. Ideally, the programme should be reverse engineered to specifically collect the data that will be needed to support the intended claims of the TPP. At the latest, it should be ready by the time writing on a submission dossier begins. Without the TPP, it can be challenging to know what aspects to focus on in the Module 2 summaries. If written in parallel, it often gets in the way of writing the dossier as the team chases a moving target. Having the TPP ready and agreed on well in advance gives the team clarity on what issues to focus on throughout the clinical programme, in general, and when writing the CTD (common technical document) summaries, in particular. During an oncology clinical programme,
it is not uncommon to have multiple dose modifications as the investigators adapt to manage AEs and slowly home in on the optimal dose regimen. Early studies can have different dosing regimens than later studies. As a result, treatment groups can be very fragmented, making it difficult to interpret the data, particularly in a pooled dataset, because the data cannot be easily compared across different doses. Changes in dosing can also mean that the proposed dose has less exposure time than earlier ones. These issues affect the interpretation of both efficacy and safety and need to be considered carefully when planning how to present the data in the dossier. Another hurdle that teams often grapple with
when writing oncology dossiers is how to handle an adverse event of special interest (AESI). Due to the different organs affected with different cancers, there is often little consistency in the AESIs collected in different studies. This presents a challenge when summarising them across studies in Module 2.7.4. Do you try to find a consistent grouping of these across studies in different cancer types, or do you just present AESIs from the pivotal trial? In oncology, the AESIs will be driven by the risk factors from the underlying disease (cancer type) and in a large dossier, you will need to find a way to bring some very diverse safety data together. This should be thought about as early as possible when the team begins to plan for the dossier, and it certainly needs to be discussed in the statistical analysis plan (SAP) for the safety summaries.
6 | Kaplan-Meier plots are widely used in oncology
programmes for the depiction of overall survival, as well as the time to onset and time to resolution of adverse events. These plots can be very useful in visualising how much of a difference there is for the duration of survival in patients treated with the drug under assessment versus other treatment options. Similarly, in the context of adverse events, Kaplan-Meier plots can help make clear the periods of risk for drug-related events. It is helpful for medical writers to understand how Kaplan-Meier plots work, so they can provide context when writing about these.
Something else to keep in mind when planning the dossiers, is whether there is a likelihood of submitting in other regions (eg Japan). If so, it is a good idea to discuss this with colleagues from those other regions, while developing the SAPs for the efficacy and safety summaries, to be sure that all analyses will be planned as required or expected by their local agencies. There is nothing more frustrating than thinking the dossier is fit-for-purpose for a global submission, only to find out that you need additional analyses to be run and incorporated. The value of having an experienced medical writer on the team is that they will be thinking about many of these challenges in advance and can bring meaningful advice and guidance to the dossier team. While subject matter experts are focused on their particular area of expertise, a medical writer is far enough away from the minute details to be able to add value to ensure the documents stay focused and fit for purpose. Medical writers often come to the project with
a fresh pair of eyes and they can ask the simple questions that the team may have overlooked. Their experience in writing submission dossiers can streamline the planning and writing process, helping the team navigate a minefield of potential problems and letting the subject matter experts spend more time on crafting the messages. With a strong regulatory lead who has a good vision of the target, and clinical experts who understand the therapeutic benefits to be gained, a strong medical writer rounds out a dossier team by advising on how to present the information in order to direct agency reviewers to what they are looking for and aid the approval process. To find out more about Trilogy Writing & Consulting, visit
www.trilogywriting.com
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