By: Tasnim Hoda, Manager of Regulatory and Medical Writing and Aaron Burr, Senior Medical Writer
The clinical development industry is an ever-changing field. It’s crucial to stay ahead of industry changes and ensure compliance with the needs of health authorities. Experienced medical writers understand the purpose of a trial and work closely with the study team to recognize efficiencies that may impact the study design or the long-term success of the clinical study.
One trial design that can lead to greater efficiencies in a clinical trial is using a master protocol.
What is a Master Protocol?
In contrast to traditional trial designs, where a single drug is tested in a single disease population in one clinical trial, master protocols use a single infrastructure, trial design, and protocol to simultaneously evaluate multiple drugs and/or disease populations in multiple substudies, allowing for efficient and accelerated drug development.
Master protocols are often categorized as:
- Basket Trials
- Umbrella Trials
- Platform Trials
Basket trials are commonly used in phase I or II of clinical drug development. This type of design uses a single investigational drug or combination studied across multiple disease populations. For example, if three different kinds of cancer being studied all share a common therapeutic or diagnostic biomarker, this trial design aims to develop a treatment driven by that biomarker.
This design can establish whether efficacy in genetic mutation in a particular site is effective in treating the same mutation in another site, leading to efficiencies in a clinical trial as there is only a single screening process for a mutation instead of screening for multiple different types.
Similar to basket trials, umbrella trials are commonly used in phase I or II of clinical drug development. This trial design evaluates multiple investigational drugs in a single disease population with potentially different genetic mutations. For example, if one disease has multiple disease or potentially-associated biomarkers.
These trials consist of many small sub-trials to test multiple drugs or treatments simultaneously in one large trial and can include multiple arms. This flexible design means that arms can be added or removed at any time.
Multiple arms allow added efficiencies in a clinical trial, leading to an improved screening success rate, rather than relying on one specific mutation like a basket trial.
Platform trials are commonly used in phase II or III in clinical drug development. In this trial design, multiple interventions can be evaluated simultaneously.
Platform trials are an extension of adaptive design trials, where multiple interventions, multiple interim evaluations, and added flexibility in the ability of new experimental arms to be added.
There are many notable differences between a traditional design and a platform design. Where traditional designs are intervention-focused, platform designs are disease-focused. Where traditional designs ask, “Can this intervention offer a benefit over the current standard of care or placebo?” platform designs ask, “What is the best intervention option for a given disease?” Finally, while traditional designs’ multi-arm trials require that all key study design features be elaborately described prior to enrollment, platform designs allow for rolling designs, where arms can be added or removed at any time.
Current Implementation of Master Protocols
Due to the emergence of biomarker-based therapy, where the goal is to “hit” a molecular target, basket and umbrella trials are most commonly used in oncology. However, the adaptability of platform trials can benefit many therapeutic areas. Master protocols have already been implemented in Influenza, Ebola, Pneumonia, and Alzheimer’s disease.
The FDA has also introduced master protocols to help with faster drug development in developing therapeutics for COVID-19. This flexibility will be helpful as, mentioned above, these trial designs can adjust with new information.
Time Saving Benefits
Many master protocols have common screening procedures, meaning there is no need to repeat data collection or screening processes for multiple separate studies. This screening platform can also identify all trials for which a patient is eligible, leading to more efficiencies for both patients and sites.
Master protocols also share governance bodies. Single governing bodies, like the Institutional Review Boards and Data Monitoring Committees, are assigned to oversee all substudies within a master protocol, enabling informed decisions about various aspects across all trials at once, instead of assessing all trials separately.
As master protocols expand to include additional therapies or therapeutic areas, study sites have shorter start-up time compared to multiple, separate trials, as most key operational features of the study have already been implemented at the site.
In addition to the time-saving benefits that come from the use of the Master Protocol, teams can additionally reduce time and effort by using the MMS SmartStart suite of tech-enabled templates, which have the ability to automatically share reusable content within and across protocols, SAPs, and CSRs.
Cost Saving Benefits
In addition to time-saving benefits, master protocols can also lead to benefits in cost savings. Site start-up and recruitment are quicker, meaning less money has to be spent on that portion of the process. During on-site monitoring visits, monitors can perform multiple trials at once, as opposed to visiting separate sites for separate trials.
Emphasis on Continuous Learning
The design of a master protocol requires collaboration between leading research, clinical experts, and regulatory agencies. This collaboration allows for sharing the latest data and real-world evidence because these protocols are always evolving.
Benefits for Patients
From a patient perspective, particularly in biomarker-driven studies, master protocols offer a more personalized treatment based on genetic makeup and biomarkers.
Keys to Successful Master Protocols
- Having a clear and consistent goal
- Early engagement with regulatory agencies, with frequent communication
- Planning and adapting to changing diseases and therapies
- Flexible systems, including study databases, simulation, and planning tools to “model” potential protocol amendments
- Keeping an open mind – stay flexible and proactive
Clinical trials may take years for outcomes to develop, but the design choice is critical for efficient drug development.
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