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So You Want to Start a Master Protocol Trial…


“Master protocols” (including platform trials, umbrella trials, and basket trials) are defined as protocols designed to answer multiple questions within the same overall trial structure. These efforts are being heralded as the pathway to less costly and more efficient clinical trials – but they are complex and often challenging to run. Patient organizations are increasingly interested in these models because they are disease-focused (rather than product-focused) and can have several positive benefits for patients. Other stakeholders are interested in engaging patient groups as partners because they can bring patient insight and participation to the table, as well as potential financial support to build the infrastructure. 

This webinar will focus on the challenges and opportunities of master protocols from the perspective of patient organizations. What lessons have been learned by those who have launched existing trials with this model? What outcomes have they achieved thus far? Join us as we discuss these questions and more to explore how master protocols could have the power to improve biomedical research and development.


  • Louis DeGennaro, President & CEO, The Leukemia & Lymphoma Society
  • Lisa LaVange, Professor and Associate Chair, and Director, Collaborative Studies Coordinating Center, Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina
  • Victoria Manax, Chief Medical Officer, Pancreatic Cancer Action Network
  • Anna Barker, Co-Director, Complex Adaptive Systems; Director, National Biomarker Development Alliance; Professor, School of Life Sciences, Arizona State University (moderator)




On December 10, FasterCures, a center of the Milken Institute, hosted a webinar titled “So You Want to Start a Master Protocol Trial.” Master protocols are an innovative model for conducting clinical trials, and they are gaining traction with regulators, product developers, and patients. These trials have the benefit of being patient-focused, time-efficient, cost-efficient, and highly collaborative. However, this model also poses challenges in the initial stages, requiring thoughtful planning and up-front collaboration and investment. The discussion focused on the advantages of conducting master protocol trials, current trials successfully using this framework, and lessons learned through implementing this trial design.

The need for a new model

FasterCures Senior Fellow Anna Barker, co-director of Complex Adaptive Systems, director of the National Biomarker Development Alliance, and professor at Arizona State University, moderated the webinar and began with an overview of master protocol trials, highlighting their significance and advantages in the research landscape.

Currently, clinical trials follow a “one-one-one” approach, where one trial seeks to answer one question about one drug. While such trials have long been the “gold standard” for clinical research and regulatory approval, Barker noted that “we are entering an era where this will no longer be sustainable”—in the era of precision medicine. One solution is conducting studies in which a single infrastructure and study design can answer multiple research questions about multiple agents more quickly and cost effectively. In other words, master protocol trials. 

Lisa LaVange, professor and associate chair, and director, Collaborative Studies Coordinating Center, Department of Biostatistics, Gillings School of Public Health, University of North Carolina, followed Barker’s introduction by explaining the three different types of master protocols: basket, umbrella, and platform. Umbrella and platform trials involve researching multiple treatments for a single disease, whereas basket trials involve researching one drug in multiple disease cohorts.

In addition to the benefits associated with the multi-tasking abilities of master protocols, LaVange noted that multiple investigations being conducted under the same umbrella can mitigate the issue of finding and potentially sharing patients for trials and can allow for more coordination in challenging research efforts. Master protocols are proving attractive in both precision medicine and rare disease trials, as they can efficiently deploy scarce eligible participants, at the same time giving patients the greatest opportunity to be placed in a trial that is most likely to benefit them.

With these benefits come initial challenges. LaVange noted that these are complex and expensive endeavors to get up and running, and she said patient advocacy groups have often been important catalysts. The U.S. Food and Drug Administration (FDA)’s vocal support (embodied in a recent guidance) has also been critical in engaging partners.

Master protocol success stories

While still relatively new, master protocol trials have already been successfully implemented and executed. Barker cited the I-SPY trials for breast cancer, one of the longest-standing master protocols, as an example of a successfully executed protocol. Since the I-SPY trial’s implementation, 1,300 patients have been enrolled in the study, 17 agents have been tested, and seven of these agents have moved to smaller phase III trials than would otherwise have been required. One drug has received accelerated approval by the FDA, while another has been given breakthrough designation. Additionally, the study has been able to validate a highly valuable surrogate endpoint that is able to be employed regardless of the drug being tested.

Adding to the master protocol success stories, Louis DeGennaro, president and CEO of The Leukemia and Lymphoma Society (LLS), told the story of “Beat AML,” a current umbrella study for adults recently diagnosed with acute myeloid leukemia (AML), an extremely lethal blood cancer that has seen no advances in treatment in 40 years. This patient-focused trial sought to determine the feasibility of implementing an umbrella study in patients with AML, the procession of patients from the master protocol to sub-studies, and the clinical efficacy of the treatments.

In the case of Beat AML, LLS holds the Investigational New Drug application, which allows it to convene all of the stakeholders needed for the study, of which there are many. Data are just now becoming available, but thus far, the trial is achieving its objectives of getting almost all patients assigned to therapy within seven days and moving patients to appropriate sub-studies. Additionally, the efficacy of the treatments observed appears to be promising.

Best practices in establishing master protocol trials

Following DeGennaro, the Pancreatic Cancer Action Network’s (PanCAN) chief medical officer, Victoria Manax, discussed her organization’s adaptive trial platform for studying pancreatic cancer. The platform, “Precision Promise,” is built with multiple study and control arms, includes patient-reported outcomes (in addition to clinical and molecular), and involves many stakeholders.

While successfully advancing the clinical trials available to patients with pancreatic cancer, Manax noted that the creation and implementation of Precision Promise faced challenges, including:

  • Infrastructure development: Multiple resources are required in developing an infrastructure, and it takes time to understand how it will best achieve the needs addressed in a study, as well as how it will fit the trial design. Strong governance and control are also necessary in determining an appropriate infrastructure in order to function on a daily basis.
  • Internal expertise: Master protocols are not like typical clinical trial designs, though having knowledge from internal staff who are familiar with clinical trials can be a useful foundation.
  • Time: There is a need to work quickly to meet the needs of the patient community, though designing and implementing master protocols require a lot of time up front. Such time includes designing a regulatory strategy plan, engaging pharmaceutical companies, and adapting to the evolving field.

Manax finalized her Precision Promise analysis and lessons learned by noting that “developing master protocols takes longer than you think, but there is no doubt that it is well worth it in the end.” Such feedback is positive, implying a promising outlook for the future of master protocol trials despite any initial challenges.


Concluding the webinar with key takeaways, Barker stressed the impact master protocol trials have on driving research and cures, as well as the importance of patient advocacy organizations in facilitating master protocol trials. With their ability to reduce study time, involve more patients, decrease costs, and better support precision medicine initiatives, master protocol trials create the option of a more sustainable structure for quickly driving science toward cures.

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