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Tumor Discovery Practice and consideration of master protocol design

protocol optimistic when none is, which will be at least budget in traditional clinical trials to establish the needed
as large as the type I error rate of each sub-study and will trial infrastructure and the increased upfront planning
increase with the number of sub-studies included . and coordination . For example, Lung-MAP is a multi-
[19]
[67]
In a basket trial, a given therapy would successively drug, multi-sub-study Master Protocol in previously
be submitted to regulators for marketing authorization in treated patients with squamous advanced non-small cell
different indications. MPWE would mean that at least one lung cancer. Funding for this study is shared between the
of the indications of therapy is declared efficacious when National Cancer Institute (NCI) and the pharmaceutical
there is no treatment effect in any of the indications. In companies at a total expected cost of $160 – 170 million
[68]
an umbrella trial, several therapies would successively be over 5 years . Therefore, the feasibility of master
submitted to regulators for marketing authorization for a protocol trials is limited even though they have lots of
similar indication. MPWE would mean that at least one advantages, such as improving efficiency, and introducing
therapy is wrongly declared efficacious in the subgroup other benefits to the staff of the trial location and local
of interest. In practice, it is logical to design a study in infrastructure. However, it is important to fund long-
which the MPWE rate is not more significant than the term master protocol trials, because they can harbor data-
equivalent error rate obtained within a series of separate driven techniques and improve the quality of clinical trial
studies. Otherwise, the correction of the MPWE rate research by building research infrastructure and improving
across different sub-studies could be needed, such as using medicine development opportunities.
smaller values of the Type I error rate in each sub-study.
8. Concluding remarks
7.3.2. The homogeneity and pooling Master protocols expedite the process of trials in late-
The subgroups of a master protocol can be considered stage drug development by testing multiple therapies
homogeneous if they share important clinical characteristics or multiple subpopulations simultaneously under a
such that the interpretation of the treatment effect and single protocol efficiently. This work aims to deepen
the assessment of the benefit/risk is meaningful for the the understanding of master protocols across various
overarching target population as a whole . In practice, diseases and therapies, providing useful information when
[19]
when target populations are too small to provide a designing and conducting master protocols. Oncology is
conclusive sample size and power, such as rare diseases, it the most prevalent field of master protocols. Thereinto,
is of great significance to make use of preplanned pooling the largest proportion is oncology drugs, which can use
among homogeneous sub-studies after an interim analysis. all types of master protocols due to the mechanism of
Homogeneity assessment depends on the strength of oncology drug action. Namely, an oncology drug usually
scientific and clinical evidence, which would influence the affects one or more specific target(s), which is consistent
execution and decision-making of the trial. For example, in with the principles of master protocols. While the demand
a basket trial that investigates a single therapy in different for clinical trials of devices is not as strong as that of drugs,
patients, if the subgroups cannot be seen as homogeneous thus the master protocol trials in oncology devices are less,
according to the assessment, the design will run a series of in which radiotherapy is the most concerned.
independent sub-studies, which leads to separate indications Besides oncology, several kinds of diseases and
and benefit/risk assessments for the same treatment. therapies may greatly benefit from master protocols, that
Otherwise, the target populations are homogeneous is, emerging infectious diseases (notably the COVID-19
enough to be considered as a whole overarching population
so that it would support a global indication and benefit/risk pandemic), rare diseases, and TCM. Relative scarce master
assessment for a target population. Notably, the adequacy protocol trials focus on fields other than oncology devices
of pooling the sub-studies and the similarity of expected reported. Each master protocols have specific principles
responses across sub-studies would need to discuss based and can be applied to various fields. For example, the
on biological and clinical grounds. platform trial accelerates the treatment evaluation for
COVID-19, which is a good way to meet the urgent
7.4. Funding limitation needs for emerging infectious diseases without effective
treatment. Umbrella or platform designs are suitable for
In clinical trials, sample size and trial duration are often
limited due to budget constraints. Therefore, the treatment rare diseases to address the rarity of the patients. Basket
designs can evaluate a single Traditional Chinese Medicine
effects or event rates might be picked with optimistic among multiple diseases with the same syndrome (Zheng).
assumptions to calculate the sample size suitable for
the budget and can stay competitive for the marketing However, due to the complexity of master protocols,
decision. Master protocol trials require more costs than the many problems and risks that are neither new nor

Volume 2 Issue 2 (2023) 16 https://doi.org/10.36922/td.342