Evidence map›Paper›PMID 31168921›Full record

ReviewDiabetes, obesity & metabolism2019

Incorporating and interpreting regulatory guidance on estimands in diabetes clinical trials: The PIONEER 1 randomized clinical trial as an example.

Vanita R Aroda, Trine Saugstrup, John B Buse, Morten Donsmark, Jeppe Zacho, Melanie J Davies

Registry-linked trialAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Diabetes, obesity & metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT02906930. Cited by 38 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 2 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.

NCT02906930 phase3completed

Efficacy and Safety of Oral Semaglutide Versus Placebo in Subjects With Type 2 Diabetes Mellitus Treated With Diet and Exercise Only.

Ran2016Enrolled703Registered outcomes48Posted comparisons18ConditionsDiabetes, Diabetes Mellitus, Type 2ArmsPlacebo, semaglutide
PMID 31186300PMID 30993900PMID 35653556PMID 34472698PMID 35373893other papers from this trial
Open the trial in the graph
3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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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

6 authors.

Vanita R ArodaDepartment of Medicine, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-7706-4585
Trine SaugstrupNovo Nordisk A/S, Søborg, Denmark.
John B BuseDepartment of Medicine, Division of Endocrinology and Metabolism, Diabetes Care Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
Morten DonsmarkNovo Nordisk A/S, Søborg, Denmark.
Jeppe ZachoNovo Nordisk A/S, Søborg, Denmark.
Melanie J DaviesDepartment of Health Sciences, Diabetes Research Centre, University of Leicester, Leicester, UK.ORCID 0000-0002-9987-9371

Funding

NCATS NIH HHS UL1 TR001102
6 · The paper itself

Abstract

Regulatory guidelines describe the use of estimands in designing and conducting clinical trials. Estimands ensure alignment of the objectives with the design, conduct and analysis of a trial. An estimand is defined by four inter-related attributes: the population of interest, the variable (endpoint) of interest, the way intercurrent events are handled and the population level summary. A trial may employ multiple estimands to evaluate treatment effects from different perspectives in order to address different scientific questions. As estimands may be an unfamiliar concept for many clinicians treating diabetes, this paper reviews the estimand concept and uses the PIONEER 1 phase 3a clinical trial, which investigated the efficacy and safety of oral semaglutide vs placebo, as an example of the way in which estimands can be implemented and interpreted. In the PIONEER 1 trial, two estimands were employed for each efficacy endpoint and were labelled as: (a) the treatment policy estimand, used to assess the treatment effect regardless of use of rescue medication or discontinuation of trial product, and provides a broad perspective of the treatment effect in the population of patients with type 2 diabetes in clinical practice; and (b) the trial product estimand, used to assess the treatment effect if all patients had continued to use trial product for the planned duration of the trial without rescue medication, thereby providing information on the anticipated treatment effect of the medication. Both approaches are complementary to understanding the effect of the studied treatments.

Indexed as

Diabetes Mellitus, Type 2Models, StatisticalRandomized Controlled Trials as TopicGlucagon-Like Peptide-1 Receptor AgonistsGlucagon-Like PeptidesHumansSemaglutideGlucagon-Like Peptide-1 Receptor AgonistsGlucagon-Like PeptidesSemaglutideDiabetesestimandGLP-1 receptor agonistsoral semaglutidePIONEERregulatory guidance

Identifiers

PMID31168921
PMCPMC6771751

What Socratic holds

Texttitle and abstract
LicenceCC BY-NC
Read underepoch 390

Registered trials

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 Socratic graph.