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Implementing the EffTox dose-finding design in the Matchpoint trial

Overview of attention for article published in BMC Medical Research Methodology, July 2017
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  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (72nd percentile)

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7 tweeters

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Title
Implementing the EffTox dose-finding design in the Matchpoint trial
Published in
BMC Medical Research Methodology, July 2017
DOI 10.1186/s12874-017-0381-x
Pubmed ID
Authors

Kristian Brock, Lucinda Billingham, Mhairi Copland, Shamyla Siddique, Mirjana Sirovica, Christina Yap

Abstract

The Matchpoint trial aims to identify the optimal dose of ponatinib to give with conventional chemotherapy consisting of fludarabine, cytarabine and idarubicin to chronic myeloid leukaemia patients in blastic transformation phase. The dose should be both tolerable and efficacious. This paper describes our experience implementing EffTox in the Matchpoint trial. EffTox is a Bayesian adaptive dose-finding trial design that jointly scrutinises binary efficacy and toxicity outcomes. We describe a nomenclature for succinctly describing outcomes in phase I/II dose-finding trials. We use dose-transition pathways, where doses are calculated for each feasible set of outcomes in future cohorts. We introduce the phenomenon of dose ambivalence, where EffTox can recommend different doses after observing the same outcomes. We also describe our experiences with outcome ambiguity, where the categorical evaluation of some primary outcomes is temporarily delayed. We arrived at an EffTox parameterisation that is simulated to perform well over a range of scenarios. In scenarios where dose ambivalence manifested, we were guided by the dose-transition pathways. This technique facilitates planning, and also helped us overcome short-term outcome ambiguity. EffTox is an efficient and powerful design, but not without its challenges. Joint phase I/II clinical trial designs will likely become increasingly important in coming years as we further investigate non-cytotoxic treatments and streamline the drug approval process. We hope this account of the problems we faced and the solutions we used will help others implement this dose-finding clinical trial design. Matchpoint was added to the European Clinical Trials Database ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-005629-65/GB ) on 2013-12-30.

Twitter Demographics

The data shown below were collected from the profiles of 7 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 18 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 18 100%

Demographic breakdown

Readers by professional status Count As %
Professor 4 22%
Student > Ph. D. Student 3 17%
Researcher 2 11%
Student > Doctoral Student 1 6%
Student > Master 1 6%
Other 1 6%
Unknown 6 33%
Readers by discipline Count As %
Mathematics 4 22%
Medicine and Dentistry 3 17%
Nursing and Health Professions 1 6%
Biochemistry, Genetics and Molecular Biology 1 6%
Unknown 9 50%

Attention Score in Context

This research output has an Altmetric Attention Score of 6. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 24 July 2017.
All research outputs
#3,734,788
of 15,767,408 outputs
Outputs from BMC Medical Research Methodology
#536
of 1,481 outputs
Outputs of similar age
#72,709
of 270,403 outputs
Outputs of similar age from BMC Medical Research Methodology
#1
of 1 outputs
Altmetric has tracked 15,767,408 research outputs across all sources so far. Compared to these this one has done well and is in the 76th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,481 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.6. This one has gotten more attention than average, scoring higher than 63% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 270,403 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 72% of its contemporaries.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them