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Review
Edward J Mills
McMaster University
Corresponding Author
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Background
Master protocols, classified as basket trials, umbrella trials, and platform trials, are a novel approach that offers enhanced efficiency and a more ethical approach to trial evaluation. Despite the many advantages of these designs, they are infrequently used.
Methods
We conducted a landscape analysis of published master protocols using a systematic literature search to determine what trials have been conducted, with an overall goal of improving literacy in this emerging concept. English-language studies identified from MEDLINE, EMBASE, and CENTRAL databases and hand-searches of published reviews and registries from inception to October 1st, 2018
Results
We identified 59 master protocols (35 basket-, 13 umbrella-, 11 platform trials). The number of master protocols has increased rapidly over the last five years. Most have been conducted in the US (n=32/59) and investigated experimental drugs (n=58/59), in the field of oncology (n=53/59). The majority of basket trials were exploratory (i.e. phase I/II; n=33/35) and not randomized (n=30/35), with half only investigating a single intervention. The median sample size of basket trials was 208 participants (Interquartile range, Q3-Q1 IQR: 589-92), with a median study duration of 60.9 (IQR: 71.9-39.9) months. Similar to basket trials, most of umbrella trials were exploratory (n=11/13), but use of randomization was more common (n=8/13). The median sample size of umbrella trials was 342 participants (IQR: 400-250), with a median study duration of 62.9 (IQR: 82.8-46.9) months. The median number of interventions investigated in umbrella trials was 5 (IQR: 5-4). In platform trials, randomization (n=10/11) and phase III investigation (n=5/10; one did not report information on phase), with four of them using seamless II/III design, were more common. The median sample size was 783.5 (IQR: 1857.5-319.5), with median study duration of 63.3 (IQR: 115.0-41.9) months.
Conclusions
We anticipate that the number of master protocols will continue to increase at a rapid pace over the upcoming decades. More efforts to improve awareness and training are needed to apply these innovative trial design methods to fields outside of oncology.
Keywords
Master protocols, basket trials, umbrella trials, platform trials, multi-arm, multi-stage design
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CURRENT STATUS: Published
View the published article at Trials.
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Editorial decision: Accept
On 19 Aug, 2019
Review #3 received
Received 14 Aug, 2019
Review #1 received
Received 13 Aug, 2019
Review #2 received
Received 11 Aug, 2019
Reviewer #3 agreed
On 05 Aug, 2019
Reviewer #2 agreed
On 03 Aug, 2019
Reviewer #1 agreed
On 02 Aug, 2019
Editor assigned
On 02 Aug, 2019
Reviewers invited
Invitations sent on 02 Aug, 2019
Submission checks complete
On 01 Aug, 2019
Version 1
Posted 02 May, 2019
No comments provided
Editorial decision: Major revision
On 08 Jul, 2019
Review #4 received
Received 03 Jul, 2019
Review #2 received
Received 02 Jul, 2019
Review #3 received
Received 02 Jul, 2019
Review #1 received
Received 27 Jun, 2019
Reviewer #4 agreed
On 20 Jun, 2019
Reviewer #3 agreed
On 14 Jun, 2019
Reviewers invited
Invitations sent on 13 Jun, 2019
Reviewer #1 agreed
On 13 Jun, 2019
Reviewer #2 agreed
On 13 Jun, 2019
Editor assigned
On 28 May, 2019
Submission checks complete
On 30 Apr, 2019
First submitted
On 11 Apr, 2019
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Interdisciplinary Medicine
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A new preprint design is coming!
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See the published version of this preprint at Trials.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Review
Edward J Mills
McMaster University
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Trials.
No community comments so far
Editorial decision: Accept
On 19 Aug, 2019
Review #3 received
Received 14 Aug, 2019
Review #1 received
Received 13 Aug, 2019
Review #2 received
Received 11 Aug, 2019
Reviewer #3 agreed
On 05 Aug, 2019
Reviewer #2 agreed
On 03 Aug, 2019
Reviewer #1 agreed
On 02 Aug, 2019
Editor assigned
On 02 Aug, 2019
Reviewers invited
Invitations sent on 02 Aug, 2019
Submission checks complete
On 01 Aug, 2019
Version 1
Posted 02 May, 2019
No comments provided
Editorial decision: Major revision
On 08 Jul, 2019
Review #4 received
Received 03 Jul, 2019
Review #2 received
Received 02 Jul, 2019
Review #3 received
Received 02 Jul, 2019
Review #1 received
Received 27 Jun, 2019
Reviewer #4 agreed
On 20 Jun, 2019
Reviewer #3 agreed
On 14 Jun, 2019
Reviewers invited
Invitations sent on 13 Jun, 2019
Reviewer #1 agreed
On 13 Jun, 2019
Reviewer #2 agreed
On 13 Jun, 2019
Editor assigned
On 28 May, 2019
Submission checks complete
On 30 Apr, 2019
First submitted
On 11 Apr, 2019
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Interdisciplinary Medicine
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Trials.
Background
Master protocols, classified as basket trials, umbrella trials, and platform trials, are a novel approach that offers enhanced efficiency and a more ethical approach to trial evaluation. Despite the many advantages of these designs, they are infrequently used.
Methods
We conducted a landscape analysis of published master protocols using a systematic literature search to determine what trials have been conducted, with an overall goal of improving literacy in this emerging concept. English-language studies identified from MEDLINE, EMBASE, and CENTRAL databases and hand-searches of published reviews and registries from inception to October 1st, 2018
Results
We identified 59 master protocols (35 basket-, 13 umbrella-, 11 platform trials). The number of master protocols has increased rapidly over the last five years. Most have been conducted in the US (n=32/59) and investigated experimental drugs (n=58/59), in the field of oncology (n=53/59). The majority of basket trials were exploratory (i.e. phase I/II; n=33/35) and not randomized (n=30/35), with half only investigating a single intervention. The median sample size of basket trials was 208 participants (Interquartile range, Q3-Q1 IQR: 589-92), with a median study duration of 60.9 (IQR: 71.9-39.9) months. Similar to basket trials, most of umbrella trials were exploratory (n=11/13), but use of randomization was more common (n=8/13). The median sample size of umbrella trials was 342 participants (IQR: 400-250), with a median study duration of 62.9 (IQR: 82.8-46.9) months. The median number of interventions investigated in umbrella trials was 5 (IQR: 5-4). In platform trials, randomization (n=10/11) and phase III investigation (n=5/10; one did not report information on phase), with four of them using seamless II/III design, were more common. The median sample size was 783.5 (IQR: 1857.5-319.5), with median study duration of 63.3 (IQR: 115.0-41.9) months.
Conclusions
We anticipate that the number of master protocols will continue to increase at a rapid pace over the upcoming decades. More efforts to improve awareness and training are needed to apply these innovative trial design methods to fields outside of oncology.
Figure 1
Figure 2
Figure 3
Figure 4
This is a list of supplementary files associated with this preprint. Click to download.
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