Oncology is one of the most common areas of drug development in the pharmaceutical industry. In 2020, the majority of new drugs approved by the FDA were cancer treatments.1,2 Existing cancer drugs are also regularly being approved for additional indications.2 The submissions needed to get these approvals are the result of large numbers of oncology studies that are being run all over the world. The summary documents for these submissions are often large and complex and having experienced medical writers working with the clinical teams, who are aware of the unique aspects of oncology studies and have an understanding of the principles underlying cancer therapies, will help pull these documents together more easily and ensure they are communicating the key messages clearly.
Cancer is a disease that is frequently treated over the long term, and even when cancer has been eliminated, follow-up continues for years. As a result, the endpoints to assess efficacy tend to look at the effect over time and its endurance, not just a static assessment of whether the disease is cured, as in many other therapeutic areas. The challenges associated with this in the context of submission dossiers arise from the fact that there are often multiple interim study reports, in addition to the final CSR, and multiple data cuts over time (sometimes with different data cuts across multiple studies, which can be tricky to explain to the reader of a submission). Cancer therapy is also a very dynamic area with developments in biotechnology rapidly shifting the approach to treatment. The medical dogma in many cancer types can shift swiftly, which means that the scientific rationale, currently available treatments, and medical need descriptions often need to be updated frequently – sometimes changing considerably, even within a 12-month period, as new treatment options change the therapeutic landscape.
The role of the medical writer in the dossier-writing process is to collaborate with the clinical experts to understand their vision for the treatment being studied and to crystallise the messaging from the clinical program. The medical writers need to come to terms with the oncology-specific terminology, acronyms and efficacy endpoints (progression-free survival, overall response rate, duration of response). They also need to work with the clinical teams to know where current changes in the medical opinion might need to be reflected in the medical need discussion and to understand how the product under assessment needs to be positioned in the overall picture of available therapies. Frequently, because the clinical experts are often deeply involved in the research going on in their area, the medical writers need to help the experts step back from the minutiae and look at the big picture in the context of a registration dossier. It is important that the regulatory documents stay focused on what is needed to get regulatory approval of the target product profile (TPP) and not get bogged down and off target in academic questions (that can be very interesting but should be saved for publications).
To do this effectively, it is essential that submission teams have a clear and well-developed TPP from the start of a clinical development program. Ideally, the program 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 program, in general, and when writing the CTD summaries, in particular.
During an oncology clinical program, 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 very 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 doses. These problems affect the interpretation of both efficacy and safety and need to be considered carefully when planning how to present the data in the dossier.