Evidence map›Paper›PMID 31533793›Full record

SynthesisTrials2019

Systematic review of basket trials, umbrella trials, and platform trials: a landscape analysis of master protocols.

Jay J H Park, Ellie Siden, Michael J Zoratti, Louis Dron, Ofir Harari, Joel Singer, Richard T Lester, Kristian Thorlund, Edward J Mills

Abstract readSystematic Review
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Trials, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 205 papers, 19 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
205citing papers in PubMed, 19 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

205 citing papers in PubMed, 19 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Pooled it
  8. Pooled it
  9. Pooled it
  10. Pooled it
  11. Pooled it
  12. Neurology · 2023
    Pooled it
  13. Pooled it
  14. Pooled it
  15. Pooled it
  16. Pooled it
  17. Pooled it
  18. Pooled it
  19. Pooled it
  20. Trial

145 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Jay J H ParkExperimental Medicine, Department of Medicine, 10th Floor, 2775 Laurel Street, Vancouver, BC, V5Z 1M9, Canada.
Ellie SidenMTEK Sciences, 802-777 West Broadway, Vancouver, BC, V5Z 1J5, Canada.
Michael J ZorattiDepartment of Health Research Methods, Evidence, and Impact, McMaster University Medical Centre, 1280 Main Street West, 2C Area, Hamilton, ON, L8S 4K1, Canada.
Louis DronMTEK Sciences, 802-777 West Broadway, Vancouver, BC, V5Z 1J5, Canada.
Ofir HarariMTEK Sciences, 802-777 West Broadway, Vancouver, BC, V5Z 1J5, Canada.
Joel SingerSchool of Population and Public Health, University of British Columbia, 2206 E Mall, Vancouver, BC, V6T 1Z3, Canada.
Richard T LesterExperimental Medicine, Department of Medicine, 10th Floor, 2775 Laurel Street, Vancouver, BC, V5Z 1M9, Canada.
Kristian ThorlundMTEK Sciences, 802-777 West Broadway, Vancouver, BC, V5Z 1J5, Canada.
Edward J MillsMTEK Sciences, 802-777 West Broadway, Vancouver, BC, V5Z 1J5, Canada. emills@mteksciences.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMaster protocols, classified as basket trials, umbrella trials, and platform trials, are novel designs that investigate multiple hypotheses through concurrent sub-studies (e.g., multiple treatments or populations or that allow adding/removing arms during the trial), offering enhanced efficiency and a more ethical approach to trial evaluation. Despite the many advantages of these designs, they are infrequently used.

methodsWe conducted a landscape analysis of master protocols using a systematic literature search to determine what trials have been conducted and proposed for an overall goal of improving the literacy in this emerging concept. On July 8, 2019, English-language studies were identified from MEDLINE, EMBASE, and CENTRAL databases and hand searches of published reviews and registries.

resultsWe identified 83 master protocols (49 basket, 18 umbrella, and 16 platform trials). The number of master protocols has increased rapidly over the last five years. Most have been conducted in the US (n = 44/83) and investigated experimental drugs (n = 82/83) in the field of oncology (n = 76/83). The majority of basket trials were exploratory (i.e., phase I/II; n = 47/49) and not randomized (n = 44/49), and more than half (n = 28/48) investigated only a single intervention. The median sample size of basket trials was 205 participants (interquartile range, Q3-Q1 [IQR]: 500-90 = 410), and the median study duration was 22.3 (IQR: 74.1-42.9 = 31.1) months. Similar to basket trials, most umbrella trials were exploratory (n = 16/18), but the use of randomization was more common (n = 8/18). The median sample size of umbrella trials was 346 participants (IQR: 565-252 = 313), and the median study duration was 60.9 (IQR: 81.3-46.9 = 34.4) months. The median number of interventions investigated in umbrella trials was 5 (IQR: 6-4 = 2). The majority of platform trials were randomized (n = 15/16), and phase III investigation (n = 7/15; one did not report information on phase) was more common in platform trials with four of them using seamless II/III design. The median sample size was 892 (IQR: 1835-255 = 1580), and the median study duration was 58.9 (IQR: 101.3-36.9 = 64.4) months.

conclusionsWe 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.

Indexed as

Clinical ProtocolsResearch DesignAdaptive Clinical Trials as TopicClinical Trials as TopicEndpoint DeterminationHumansTreatment OutcomeBasket trialsMaster protocolsMulti-arm, multi-stage designPlatform trialsUmbrella trials

Identifiers

PMID31533793
PMCPMC6751792

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.