Master protocol studies have been taking over and playing a fundamental part in what is considered the “new normal” in clinical research; providing actionable data to support health policy and resourcing. Due to the fast influx of master protocols, Medical Writers will be expected to become fluent in study protocols. Adoption of master protocols soon came to the forefront during the COVID-19 emergence. The way that the study designs showed structure and sustainable approaches to clinical research allowed for enhanced efficiency and uniformity. So, what exactly is a master protocol study? Master protocol studies cannot be characterized by one definition but are rather characterized by multiple parallel studies that share a common overarching framework.  

Choosing the right fit for clinical study protocol structure

Study protocols that demonstrate to be too complex can have extended disrupting results. Similarly, overly burdensome protocol can lead to study sites redirecting participants to other more preferable studies and participant dropout rates in excess of 30%. On the other hand, master protocol studies are conducted through operational implementation, using a process that uses critically thinking to decide how multiple substudies are submitted, updated, and reported.

Flexibility is crucial for protocol development

Selecting the Development Team

Establishing the study team is an important part prior to protocol development. By doing this, the team can begin understanding individual expertise and discussing study objectives. Unlike today’s traditional studies, identifying all study team members prior to the protocol development can be challenging since the team structure is reliant on on the complete study design, number of interventions, and regions involved.

Agreeing on the protocol structure

One of the most important parts prior to initiating protocol development is ensuring all team members have reviewed and agree on the protocol structure. This will reduce the risk of conflicting opinions, leading to extended review cycles or require multiple document drafts. To help identify the best suitable protocol, the Medical Writer can initiate early discussions. To help support, key questions the Medical Writer can ask are:

• Does the master protocol structure give clarity and coherency for readers?
• Will information be repeated, or will a single source of information be noted throughout?
• What information varies from core protocol to subprotocol?

Once the protocol structure has been decided, the Medical Writer can create a protocol scaffold to outline what the team’s structure will be. By creating such outline, the Medical Writer reduces the risk of the study team rejecting the protocol structure during the team’s revision; thus, demanding multiple changes throughout the protocol’s development.

Establishing, and maintaining, timelines

In conjunction to agreement on protocol structure and scaffold, aligning on timelines is vital to setting team and individual expectations. There are two approaches to consider:

• Parallel approach: Similar to today’s traditional protocol development, allowing for adequate time for content development and reviews
• Staggered approach: leading content, such as core protocol, is initially submitted for review, followed by trailing content, or subprotocols

There are many considerations when deciding traditional verse master protocol structures, but with the post-pandemic world we understand that master protocols are evolving alongside clinical research. The complexity and variability in the accompanying protocol development process can test even the most experienced Medical Writer and study team. Therefore, what was known as the standard protocol templates are becoming insufficient for addressing the intricacy of master protocols.