Abstract:New diagnostics are urgently needed to address emerging antimicrobial resistance. The Antibacterial Resistance Leadership Group proposes a strategy called MASTERMIND (Master Protocol for Evaluating Multiple Infection Diagnostics) for advancement of infectious diseases diagnostics. The goal of this strategy is to generate the data necessary to support US Food and Drug Administration clearance of new diagnostic tests by promoting research that might not have otherwise been feasible with conventional trial design… Show more
“…This requires standardization of the microbiological and molecular approach to isolate analysis between China and the United States, which is currently ongoing. MASTER Protocol for Multiple Infection Diagnostics (MASTERMIND) [24] Abbreviations: CRACKLE, Consortium on Resistance Against Carbapenems in Klebsiella and Enterobacteriaceae; CRAb, carbapenem-resistant Acinetobacter baumannii; CRE, carbapenem-resistant Enterobacteriaceae; RCT, randomized controlled trial.…”
A strong synergy can result from China-US antimicrobial resistance (AMR) collaborations given similarities and differences between their respective healthcare systems and research infrastructures. The Antibacterial Resistance Leadership Group has employed a model of realistic growth, starting with a feasible, relatively low-resource observational study in a critical priority pathogen. This and other observational studies will provide vital scientific information required for the rational design of future interventional trials. In addition, it provides a mutual, low-risk opportunity for determining the strengths and opportunities of the research collaboration. Issues identified during the observational studies can be addressed prior to the initiation of high-resource interventional studies. Collaborative clinical AMR studies between China and the United States have tremendous potential to decrease AMR rates, improve responsible antibiotic use, and ultimately improve the lives of patients in both countries.
“…This requires standardization of the microbiological and molecular approach to isolate analysis between China and the United States, which is currently ongoing. MASTER Protocol for Multiple Infection Diagnostics (MASTERMIND) [24] Abbreviations: CRACKLE, Consortium on Resistance Against Carbapenems in Klebsiella and Enterobacteriaceae; CRAb, carbapenem-resistant Acinetobacter baumannii; CRE, carbapenem-resistant Enterobacteriaceae; RCT, randomized controlled trial.…”
A strong synergy can result from China-US antimicrobial resistance (AMR) collaborations given similarities and differences between their respective healthcare systems and research infrastructures. The Antibacterial Resistance Leadership Group has employed a model of realistic growth, starting with a feasible, relatively low-resource observational study in a critical priority pathogen. This and other observational studies will provide vital scientific information required for the rational design of future interventional trials. In addition, it provides a mutual, low-risk opportunity for determining the strengths and opportunities of the research collaboration. Issues identified during the observational studies can be addressed prior to the initiation of high-resource interventional studies. Collaborative clinical AMR studies between China and the United States have tremendous potential to decrease AMR rates, improve responsible antibiotic use, and ultimately improve the lives of patients in both countries.
“…There were four key characteristics found among the 20 unique definitions of master protocols (Fig. 1) [[12], [13], [14], [15], [16]] [[1], [2], [3], [4], [5],8,[17], [18], [19], [20], [21], [22]]. While all sources consistently highlighted that common infrastructure is essential for master protocols, there were some variation with respect to scope, shared ethics review, and centralized data monitoring.…”
Section: Resultsmentioning
confidence: 99%
“…the reported definitions pertained to oncology or a specific area in oncology only), limiting master protocols to the field of oncology. Only a few definitions specified shared ethics review structures (n = 2) [13,22] and centralized data monitoring (n = 4) [1,2,16,20] as integral to master protocols.Fig. 1 Master protocol definition characteristics .…”
Background
In September 2018 the FDA provided a draft guidance on master protocols reflecting an increased interest in these designs by industry. Master protocols refer to a single overarching protocol developed to evaluate multiple hypotheses and may be further categorized as basket, umbrella, and platform trials. However, inconsistencies in reporting persist in the literature. We conducted a systematic review to describe master protocol reporting with the goal of facilitating the further development and spread of these innovative trial designs.
Methods
We searched MEDLINE, EMBASE, and CENTRAL from inception to April 25, 2019 for English articles on master protocols. This was supplemented by hand searches of trial registries and of the bibliographies of published reviews. We used the FDA's definitions of master protocols as references and compared them to self-reported master protocols.
Results
We identified 278 master protocol publications, consisting of 228 protocols and 50 reviews. Sixty-six records provided unique definitions of master protocol types. We observed considerable heterogeneity in definitions of master protocols, and over half (54%) used oncology-specific language. The majority of self-classified master protocols (57%) were consistent with the FDA's definitions of master protocols.
Conclusion
The terms ‘master protocol’, ‘basket trial’, ‘umbrella trial’, and ‘platform trial’ are inconsistently described. Careful treatment of these terms and adherence to the definitions set forth by the FDA will facilitate better understanding of these trial designs and allow them to be used broadly and to their full potential in clinical research. We encourage trial methodologists to use these trial designations when applicable.
“…Future research will have to show how host-based diagnostics can complement advanced pathogen-based diagnostics. Blinded, prospective studies are key to establishing accuracy, but randomized interventional outcomes studies will be necessary to fully show the potential clinical value [33,34]. Nevertheless, we believe that the hospital of the future is likely to have a three-pronged approach to diagnosing sepsis, including (1) rapid host-based screening and diagnostic tests that are run at or near the point of care that can inform whether to treat patients with antibiotics, what downstream diagnostics are needed, and at what level of care; (2) rapid sample-toanswer ID and AST tests that can definitively identify therapy for patients that screen positive with host-response tests, and (3) longer culture-based or novel next-generation sequencing tests for patients with persistent illness despite (1) and (2).…”
Section: Probing the Host Response As An Alternative Approach To Diagmentioning
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